Antioxidants

18 pages, 2067 KiB

Open AccessArticle

New Lipophenol Antioxidants Reduce Oxidative Damage in Retina Pigment Epithelial Cells

by Espérance Moine, Philippe Brabet, Laurent Guillou, Thierry Durand, Joseph Vercauteren and Céline Crauste

Antioxidants 2018, 7(12), 197; https://doi.org/10.3390/antiox7120197 - 19 Dec 2018

Cited by 30 | Viewed by 5100

Abstract

Age-related macular degeneration (AMD) is a multifactorial pathology and its progression is exacerbated by oxidative stress. Oxidation and photo-oxidation reactions modify lipids in retinal cells, contribute to tissue injury, and lead to the formation of toxic adducts. In particular, autofluorescent pigments such as [...] Read more.

Age-related macular degeneration (AMD) is a multifactorial pathology and its progression is exacerbated by oxidative stress. Oxidation and photo-oxidation reactions modify lipids in retinal cells, contribute to tissue injury, and lead to the formation of toxic adducts. In particular, autofluorescent pigments such as N-retinylidene-N-retinylethanolamine (A2E) accumulate as lipofuscin in retinal pigment epithelial cells, contribute to the production of additional reactive oxygen species (ROS), and lead to cell degeneration. In an effort to develop efficient antioxidants to reduce damage caused by lipid oxidation, various natural polyphenols were structurally modified to increase their lipophilicity (lipophenols). In this study, resveratrol, phloroglucinol, quercetin and catechin were selected and conjugated to various polyunsaturated fatty acids (PUFAs) using classical chemical strategies or enzymatic reactions. After screening for cytotoxicity, the capacity of the synthesized lipophenols to reduce ROS production was evaluated in ARPE-19 cells subjected to H₂O₂ treatment using a dichlorofluorescein diacetate probe. The positions of the PUFA on the polyphenol core appear to influence the antioxidant effect. In addition, two lipophenolic quercetin derivatives were evaluated to highlight their potency in protecting ARPE-19 cells against A2E photo-oxidation toxicity. Quercetin conjugated to linoleic or α-linolenic acid were promising lipophilic antioxidants, as they protected ARPE-19 cells from A2E-induced cell death more effectively than the parent polyphenol, quercetin. Full article

(This article belongs to the Special Issue Lipid Peroxidation: Analysis and Applications in Biological Systems)

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12 pages, 336 KiB

Open AccessReview

Monocyte Subsets in Atherosclerosis and Modification with Exercise in Humans

by Ning Hong Aw, Elisa Canetti, Katsuhiko Suzuki and Jorming Goh

Antioxidants 2018, 7(12), 196; https://doi.org/10.3390/antiox7120196 - 19 Dec 2018

Cited by 26 | Viewed by 9809

Abstract

Atherosclerosis is a progressive pathological remodeling of the arteries and one of its hallmarks is the presence of chronic inflammation. Notably, there is an increased proportion and activation state of specific monocyte subsets in systemic blood circulation. Monocyte subsets have distinct contributions to [...] Read more.

Atherosclerosis is a progressive pathological remodeling of the arteries and one of its hallmarks is the presence of chronic inflammation. Notably, there is an increased proportion and activation state of specific monocyte subsets in systemic blood circulation. Monocyte subsets have distinct contributions to the formation, progression, and destabilization of the atherosclerotic plaque. Strong clinical and epidemiological studies show that regular aerobic exercise mitigates the progression of cardiovascular disease. In fact, aerobic fitness is a powerful predictor of cardiovascular mortality in adults, independent of traditional risk factors such as hypertension and hyperlipidemia. Acute bouts and chronic exercise training modulate monocyte behavior, ranging from their recruitment from the bone marrow or marginal pool, to tissue margination and functional changes in cytokine and chemokine production. Such modulation could reflect a potential mechanism for the cardio-protective effect of exercise on atherosclerosis. This review summarizes the current knowledge of monocyte subsets and highlights what is known about their responses to exercise. Full article

(This article belongs to the Special Issue Exercise and Inflammation)

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27 pages, 1011 KiB

Open AccessReview

Adrenergic Regulation of Drp1-Driven Mitochondrial Fission in Cardiac Physio-Pathology

by Bong Sook Jhun, Jin O-Uchi, Stephanie M. Adaniya, Michael W. Cypress and Yisang Yoon

Antioxidants 2018, 7(12), 195; https://doi.org/10.3390/antiox7120195 - 18 Dec 2018

Cited by 33 | Viewed by 11433

Abstract

Abnormal mitochondrial morphology, especially fragmented mitochondria, and mitochondrial dysfunction are hallmarks of a variety of human diseases including heart failure (HF). Although emerging evidence suggests a link between mitochondrial fragmentation and cardiac dysfunction, it is still not well described which cardiac signaling pathway [...] Read more.

Abnormal mitochondrial morphology, especially fragmented mitochondria, and mitochondrial dysfunction are hallmarks of a variety of human diseases including heart failure (HF). Although emerging evidence suggests a link between mitochondrial fragmentation and cardiac dysfunction, it is still not well described which cardiac signaling pathway regulates mitochondrial morphology and function under pathophysiological conditions such as HF. Mitochondria change their shape and location via the activity of mitochondrial fission and fusion proteins. This mechanism is suggested as an important modulator for mitochondrial and cellular functions including bioenergetics, reactive oxygen species (ROS) generation, spatiotemporal dynamics of Ca²⁺ signaling, cell growth, and death in the mammalian cell- and tissue-specific manners. Recent reports show that a mitochondrial fission protein, dynamin-like/related protein 1 (DLP1/Drp1), is post-translationally modified via cell signaling pathways, which control its subcellular localization, stability, and activity in cardiomyocytes/heart. In this review, we summarize the possible molecular mechanisms for causing post-translational modifications (PTMs) of DLP1/Drp1 in cardiomyocytes, and further discuss how these PTMs of DLP1/Drp1 mediate abnormal mitochondrial morphology and mitochondrial dysfunction under adrenergic signaling activation that contributes to the development and progression of HF. Full article

(This article belongs to the Special Issue Mitochondrial Shape Change in Physio-Pathology)

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10 pages, 1005 KiB

Open AccessArticle

Suppressing Effect of 2-Nitrobenzaldehyde on Singlet Oxygen Generation, Fatty Acid Photooxidation, and Dye-Sensitizer Degradation

by Mahdi Hajimohammadi, Atena Vaziri Sereshk, Clemens Schwarzinger and Günther Knör

Antioxidants 2018, 7(12), 194; https://doi.org/10.3390/antiox7120194 - 18 Dec 2018

Cited by 7 | Viewed by 4544

Abstract

2-Nitrobenzaldehyde was found to efficiently block singlet oxygen generation in a series of different test samples upon exposure to UV and visible light under aerobic conditions. The effect of quenching singlet oxygen formation was monitored in the presence of 1, 4-diazabicyclo [2.2.2] octane [...] Read more.

2-Nitrobenzaldehyde was found to efficiently block singlet oxygen generation in a series of different test samples upon exposure to UV and visible light under aerobic conditions. The effect of quenching singlet oxygen formation was monitored in the presence of 1, 4-diazabicyclo [2.2.2] octane (DABCO) acting as a well-known singlet oxygen scavenger. A comparison of different nitrobenzaldehyde isomers with other highly effective synthetic antioxidants used in the food industry such as butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), tert-butylhydroquinone (TBHQ) revealed that the protection of materials from singlet oxygen decreases in the order of 2-nitrobenzaldehyde > DABCO > TBHQ > 3-nitrobenzaldehyde > BHA > 4-nitrobenzaldehyde > BHT. Upon addition of 2-nitrobenzaldehyde, the oxidation of fatty acids and the degradation of photosensitizers was found to be considerably diminished, which indicates that the presence of 2-nitrobenzaldehyde has a significant protective influence by restricting the singlet oxygen generation and photodegradation of dyes. Moreover, the compound turned out to display its highly suppressing effects on typical singlet oxygen-dependent reactions, such as fatty acid photooxidation and dye photosensitizer degradation, in a rather broad spectral region covering wavelengths from 300 nm (UV-B) to 575 nm (close to the maximum of ambient solar radiation). Full article

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13 pages, 826 KiB

Open AccessReview

Oxidative Stress in the Newborn Period: Useful Biomarkers in the Clinical Setting

by Iván Millán, José David Piñero-Ramos, Inmaculada Lara, Anna Parra-Llorca, Isabel Torres-Cuevas and Máximo Vento

Antioxidants 2018, 7(12), 193; https://doi.org/10.3390/antiox7120193 - 14 Dec 2018

Cited by 40 | Viewed by 6081

Abstract

Aerobic metabolism is highly efficient in providing energy for multicellular organisms. However, even under physiological conditions, an incomplete reduction of oxygen produces reactive oxygen species and, subsequently, oxidative stress. Some of these chemical species are highly reactive free radicals capable of causing functional [...] Read more.

Aerobic metabolism is highly efficient in providing energy for multicellular organisms. However, even under physiological conditions, an incomplete reduction of oxygen produces reactive oxygen species and, subsequently, oxidative stress. Some of these chemical species are highly reactive free radicals capable of causing functional and structural damage to cell components (protein, lipids, or nucleotides). Oxygen is the most used drug in ill-adapted patients during the newborn period. The use of oxygen may cause oxidative stress-related diseases that increase mortality and cause morbidity with adverse long-term outcomes. Conditions such as prematurity or birth asphyxia are frequently treated with oxygen supplementation. Both pathophysiological situations of hypoxia–reoxygenation in asphyxia and hyperoxia in premature infants cause a burst of reactive oxygen species and oxidative stress. Recently developed analytical assays using mass spectrometry have allowed us to determine highly specific biomarkers with minimal samples. The detection of these metabolites will help improve the diagnosis, evolution, and response to therapy in oxidative stress-related conditions during the newborn period. Full article

(This article belongs to the Special Issue Lipid Peroxidation: Analysis and Applications in Biological Systems)

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11 pages, 2276 KiB

Open AccessArticle

Agrimonia procera Wallr. Extract Increases Stress Resistance and Prolongs Life Span in Caenorhabditis elegans via Transcription Factor DAF-16 (FoxO Orthologue)

by Christina Saier, Inge Gommlich, Volker Hiemann, Sabrina Baier, Karoline Koch, Gert Horn, Tanja Kowalewsky, Jörg Bartelt, Maria Seemann and Wim Wätjen

Antioxidants 2018, 7(12), 192; https://doi.org/10.3390/antiox7120192 - 14 Dec 2018

Cited by 15 | Viewed by 4182

Abstract

Agrimonia procera is a pharmacologically interesting plant which is proposed to protect against various diseases due to its high amount of phytochemicals, e.g., polyphenols. However, in spite of the amount of postulated health benefits, studies concerning the mechanistic effects of Agrimonia procera are [...] Read more.

Agrimonia procera is a pharmacologically interesting plant which is proposed to protect against various diseases due to its high amount of phytochemicals, e.g., polyphenols. However, in spite of the amount of postulated health benefits, studies concerning the mechanistic effects of Agrimonia procera are limited. Using the nematode Caenorhabditis elegans, we were able to show that an ethanol extract of Agrimonia procera herba (eAE) mediates strong antioxidative effects in the nematode: Beside a strong radical-scavenging activity, eAE reduces accumulation of reactive oxygen species (ROS) accumulation and protects against paraquat-induced oxidative stress. The extract does not protect against amyloid-β-mediated toxicity, but efficiently increases the life span (up to 12.7%), as well as the resistance to thermal stress (prolongation of survival up to 22%), of this model organism. Using nematodes deficient in the forkhead box O (FoxO)-orthologue DAF-16, we were able to demonstrate that beneficial effects of eAE on stress resistance and life span were mediated via this transcription factor. We showed antioxidative, stress-reducing, and life-prolonging effects of eAE in vivo and were able to demonstrate a molecular mechanism of this extract. These results may be important for identifying further molecular targets of eAE in humans. Full article

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22 pages, 2006 KiB

Open AccessReview

The Oxidized Protein Repair Enzymes Methionine Sulfoxide Reductases and Their Roles in Protecting against Oxidative Stress, in Ageing and in Regulating Protein Function

by Sofia Lourenço dos Santos, Isabelle Petropoulos and Bertrand Friguet

Antioxidants 2018, 7(12), 191; https://doi.org/10.3390/antiox7120191 - 12 Dec 2018

Cited by 62 | Viewed by 7525

Abstract

Cysteine and methionine residues are the amino acids most sensitive to oxidation by reactive oxygen species. However, in contrast to other amino acids, certain cysteine and methionine oxidation products can be reduced within proteins by dedicated enzymatic repair systems. Oxidation of cysteine first [...] Read more.

Cysteine and methionine residues are the amino acids most sensitive to oxidation by reactive oxygen species. However, in contrast to other amino acids, certain cysteine and methionine oxidation products can be reduced within proteins by dedicated enzymatic repair systems. Oxidation of cysteine first results in either the formation of a disulfide bridge or a sulfenic acid. Sulfenic acid can be converted to disulfide or sulfenamide or further oxidized to sulfinic acid. Disulfide can be easily reversed by different enzymatic systems such as the thioredoxin/thioredoxin reductase and the glutaredoxin/glutathione/glutathione reductase systems. Methionine side chains can also be oxidized by reactive oxygen species. Methionine oxidation, by the addition of an extra oxygen atom, leads to the generation of methionine sulfoxide. Enzymatically catalyzed reduction of methionine sulfoxide is achieved by either methionine sulfoxide reductase A or methionine sulfoxide reductase B, also referred as to the methionine sulfoxide reductases system. This oxidized protein repair system is further described in this review article in terms of its discovery and biologically relevant characteristics, and its important physiological roles in protecting against oxidative stress, in ageing and in regulating protein function. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)

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9 pages, 1191 KiB

Open AccessArticle

New Insights into the Potential of Endogenous Redox Systems in Wheat Bread Dough

by Nicolas Navrot, Rikke Buhl Holstborg, Per Hägglund, Inge Lise Povlsen and Birte Svensson

Antioxidants 2018, 7(12), 190; https://doi.org/10.3390/antiox7120190 - 12 Dec 2018

Cited by 5 | Viewed by 3300

Abstract

Various redox compounds are known to influence the structure of the gluten network in bread dough, and hence its strength. The cereal thioredoxin system (NTS), composed of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent thioredoxin reductase (NTR) and thioredoxin (Trx), is a major reducing enzymatic [...] Read more.

Various redox compounds are known to influence the structure of the gluten network in bread dough, and hence its strength. The cereal thioredoxin system (NTS), composed of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent thioredoxin reductase (NTR) and thioredoxin (Trx), is a major reducing enzymatic system that is involved in seed formation and germination. NTS is a particularly interesting tool for food processing due to its heat stability and its broad range of protein substrates. We show here that barley NTS is capable of remodeling the gluten network and weakening bread dough. Furthermore, functional wheat Trx that is present in the dough can be recruited by the addition of recombinant barley NTR, resulting in dough weakening. These results confirm the potential of NTS, especially NTR, as a useful tool in baking for weakening strong doughs, or in flat product baking. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)

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9 pages, 1660 KiB

Open AccessArticle

Far Infrared Irradiation Enhances Nutraceutical Compounds and Antioxidant Properties in Angelica gigas Nakai Powder

by Md Obyedul Kalam Azad, Jing Pei Piao, Cheol Ho Park and Dong Ha Cho

Antioxidants 2018, 7(12), 189; https://doi.org/10.3390/antiox7120189 - 11 Dec 2018

Cited by 18 | Viewed by 3729

Abstract

The aim of this study was to investigate the effect of far infrared irradiation (FIR) on nutraceutical compounds, viz. total phenolic content, total flavonoids, and antioxidant capacity, of Angelica gigas Nakai (AGN). The FIR treatment was applied for 30 min with varied temperatures [...] Read more.

The aim of this study was to investigate the effect of far infrared irradiation (FIR) on nutraceutical compounds, viz. total phenolic content, total flavonoids, and antioxidant capacity, of Angelica gigas Nakai (AGN). The FIR treatment was applied for 30 min with varied temperatures of 120, 140, 160, 180, 200, 220, and 240 °C. Results showed that FIR increased total phenolic and flavonoid content in AGN at 220 °C. The HPLC results revealed higher quantities of decursin (62.48 mg/g) and decursinol angelate (41.51 mg/g) at 220 °C compared to control (38.70 mg/g, 27.54 mg/g, respectively). The antioxidant capacity of AGN was also increased at 220 °C, as measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and the phosphomolybdenum (PPMD) method. A further increase of the FIR temperature caused a reduction of compound content. In addition, the results also showed a strong correlation between phenolic content and antioxidant properties of AGN powder. These findings will help to further improve the nutraceutical profile of AGN powder by optimizing the FIR conditions. Full article

(This article belongs to the Special Issue Antioxidant Activity of Polyphenolic Plant Extracts)

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12 pages, 2150 KiB

Open AccessArticle

Novel Docosahexaenoic Acid Ester of Phloridzin Inhibits Proliferation and Triggers Apoptosis in an In Vitro Model of Skin Cancer

by Theodora Mantso, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, H. P. Vasantha Rupasinghe and Mihalis I. Panayiotidis

Antioxidants 2018, 7(12), 188; https://doi.org/10.3390/antiox7120188 - 11 Dec 2018

Cited by 10 | Viewed by 4356

Abstract

Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation [...] Read more.

Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation of liver, breast, and blood cancer cell lines. In the present study, we investigated the cytotoxic potential of PZDHA in an in vitro model of skin cancer consisting of melanoma (A375), epidermoid carcinoma (A431), and non-tumorigenic (HaCaT) cell lines. Decosahexaenoic acid ester of phloridzin led to increased cytotoxicity in all cell lines as revealed by cell viability assays. However, growth inhibition and induction of both apoptosis and necrosis was more evident in melanoma (A375) and epidermoid carcinoma (A431) cells, whereas non-tumorigenic keratinocytes (HaCaT) appeared to be more resistant as detected by flow cytometry. More specifically, PZDHA-induced cell cycle growth arrest at the G2/M phase in A375 and A431 cells in contrast to HaCaT cells, which were growth arrested at the G0/G1 phase. Elevated intracellular generation of reactive oxygen species ROS was detected in all cell lines. Overall, our findings support the potential of PZDHA as a novel therapeutic means against human skin cancer. Full article

(This article belongs to the Special Issue Dietary Antioxidants in Cancer Chemoprevention)

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27 pages, 711 KiB

Open AccessReview

Flavonoids and Colorectal Cancer Prevention

by Yanyan Li, Tao Zhang and Grace Y. Chen

Antioxidants 2018, 7(12), 187; https://doi.org/10.3390/antiox7120187 - 10 Dec 2018

Cited by 58 | Viewed by 10103

Abstract

Colorectal cancer (CRC) is the third most common cancer, but despite advances in treatment, it remains the second most common cause of cancer-related mortality. Prevention may, therefore, be a key strategy in reducing colorectal cancer deaths. Given reports of an inverse association between [...] Read more.

Colorectal cancer (CRC) is the third most common cancer, but despite advances in treatment, it remains the second most common cause of cancer-related mortality. Prevention may, therefore, be a key strategy in reducing colorectal cancer deaths. Given reports of an inverse association between fruit and vegetable consumption with colorectal cancer risk, there has been significant interest in understanding the metabolism and bioactivity of flavonoids, which are highly abundant in fruits and vegetables and account for their pigmentation. In this review, we discuss host and microbiota-mediated metabolism of flavonoids and the potential mechanisms by which flavonoids can exert protective effects against colon tumorigenesis, including regulation of signaling pathways involved in apoptosis, cellular proliferation, and inflammation and modulation of the gut microbiome. Full article

(This article belongs to the Special Issue Flavonoids: Immune-Regulation and Health)

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21 pages, 1510 KiB

Open AccessReview

Mitochondrial Membrane Dynamics—Functional Positioning of OPA1

by Hakjoo Lee and Yisang Yoon

Antioxidants 2018, 7(12), 186; https://doi.org/10.3390/antiox7120186 - 8 Dec 2018

Cited by 43 | Viewed by 9927

Abstract

The maintenance of mitochondrial energetics requires the proper regulation of mitochondrial morphology, and vice versa. Mitochondrial dynamins control mitochondrial morphology by mediating fission and fusion. One of them, optic atrophy 1 (OPA1), is the mitochondrial inner membrane remodeling protein. OPA1 has a dual [...] Read more.

The maintenance of mitochondrial energetics requires the proper regulation of mitochondrial morphology, and vice versa. Mitochondrial dynamins control mitochondrial morphology by mediating fission and fusion. One of them, optic atrophy 1 (OPA1), is the mitochondrial inner membrane remodeling protein. OPA1 has a dual role in maintaining mitochondrial morphology and energetics through mediating inner membrane fusion and maintaining the cristae structure. OPA1 is expressed in multiple variant forms through alternative splicing and post-translational proteolytic cleavage, but the functional differences between these variants have not been completely understood. Recent studies generated new information regarding the role of OPA1 cleavage. In this review, we will first provide a brief overview of mitochondrial membrane dynamics by describing fission and fusion that are mediated by mitochondrial dynamins. The second part describes OPA1-mediated fusion and energetic maintenance, the role of OPA1 cleavage, and a new development in OPA1 function, in which we will provide new insight for what OPA1 does and what proteolytic cleavage of OPA1 is for. Full article

(This article belongs to the Special Issue Mitochondrial Shape Change in Physio-Pathology)

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14 pages, 2386 KiB

Open AccessArticle

Effect of Agraz (Vaccinium meridionale Swartz) on High-Density Lipoprotein Function and Inflammation in Women with Metabolic Syndrome

by Catalina Marín-Echeverri, Christopher N. Blesso, Maria Luz Fernández, Yeisson Galvis-Pérez, Gelmy Ciro-Gómez, Vitelbina Núñez-Rangel, Juan C. Aristizábal and Jacqueline Barona-Acevedo

Antioxidants 2018, 7(12), 185; https://doi.org/10.3390/antiox7120185 - 8 Dec 2018

Cited by 16 | Viewed by 5249

Abstract

Metabolic syndrome (MetS) is associated with low-grade inflammation and high-density lipoprotein (HDL) dysfunction. Polyphenol-rich foods may improve these alterations. Agraz is a fruit rich in polyphenols (mainly anthocyanins); however, there is limited information about its effects on human health. We evaluated the effects [...] Read more.

Metabolic syndrome (MetS) is associated with low-grade inflammation and high-density lipoprotein (HDL) dysfunction. Polyphenol-rich foods may improve these alterations. Agraz is a fruit rich in polyphenols (mainly anthocyanins); however, there is limited information about its effects on human health. We evaluated the effects of agraz consumption as compared to placebo on HDL function and inflammation in women with MetS. Forty volunteers (25–60 years) were included in this double-blind crossover study. Women consumed agraz or placebo over 4 weeks; separated by a 4-week washout period. HDL function (apoliprotein-A1; paraoxonase 1 (PON1) activity; cholesterol efflux capacity), oxidative stress (myeloperoxidase (MPO), advanced oxidation protein products) and inflammatory markers (serum cytokines/chemokines and peripheral blood mononuclear cell nuclear factor-kB) were measured after each period. Compared to placebo, agraz consumption did not significantly change any of the biomarkers measured. Interestingly, only after agraz period there were significant positive correlations between PON1 activities and cholesterol efflux. Additionally, there were significant inverse correlations between changes in inflammatory markers and HDL function markers and positive correlations with oxidative markers. Although polyphenol-rich foods have been shown to be beneficial for certain conditions; polyphenol-rich agraz fruit consumption did not impact inflammation and HDL function in the current study of women with MetS. Full article

(This article belongs to the Special Issue Antioxidants in Oxidative Stress Diseases)

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15 pages, 812 KiB

Open AccessArticle

Evaluation of Antioxidant, Anti-Inflammatory and Cytoprotective Properties of Ethanolic Mint Extracts from Algeria on 7-Ketocholesterol-Treated Murine RAW 264.7 Macrophages

by Fatiha Brahmi, Thomas Nury, Meryam Debbabi, Samia Hadj-Ahmed, Amira Zarrouk, Michel Prost, Khodir Madani, Lila Boulekbache-Makhlouf and Gérard Lizard

Antioxidants 2018, 7(12), 184; https://doi.org/10.3390/antiox7120184 - 6 Dec 2018

Cited by 36 | Viewed by 5859

Abstract

The present study consisted in evaluating the antioxidant, anti-inflammatory and cytoprotective properties of ethanolic extracts from three mint species (Mentha spicata L. (MS), Mentha pulegium L. (MP) and Mentha rotundifolia (L.) Huds (MR)) with biochemical methods on murine RAW 264.7 macrophages (a [...] Read more.

The present study consisted in evaluating the antioxidant, anti-inflammatory and cytoprotective properties of ethanolic extracts from three mint species (Mentha spicata L. (MS), Mentha pulegium L. (MP) and Mentha rotundifolia (L.) Huds (MR)) with biochemical methods on murine RAW 264.7 macrophages (a transformed macrophage cell line isolated from ascites of BALB/c mice infected by the Abelson leukemia virus). The total phenolic, flavonoid and carotenoid contents were determined with spectrophotometric methods. The antioxidant activities were quantified with the Kit Radicaux Libres (KRL^TM), the ferric reducing antioxidant power (FRAP) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The MS extract showed the highest total phenolic content, and the highest antioxidant capacity, while the MR extract showed the lowest total phenolic content and the lowest antioxidant capacity. The cytoprotective and anti-inflammatory activities of the extracts were quantified on murine RAW 264.7 macrophages treated with 7-ketocholesterol (7KC; 20 µg/mL: 50 µM) associated or not for 24 h and 48 h with ethanolic mint extracts used at different concentrations (25, 50, 100, 200 and 400 µg/mL). Under treatment with 7KC, an important inhibition of cell growth was revealed with the crystal violet test. This side effect was strongly attenuated in a dose dependent manner with the different ethanolic mint extracts, mainly at 48 h. The most important cytoprotective effect was observed with the MS extract. In addition, the effects of ethanolic mint extracts on cytokine secretion (Interleukin (IL)-6, IL-10, Monocyte Chemoattractant Protein (MCP)-1, Interferon (IFN)-ϒ, Tumor necrosis factor (TNF)-α) were determined at 24 h on lipopolysaccharide (LPS, 0.2 µg/mL)-, 7KC (20 µg/mL)- and (7KC + LPS)-treated RAW 264.7 cells. Complex effects of mint extracts were observed on cytokine secretion. However, comparatively to LPS-treated cells, all the extracts strongly reduce IL-6 secretion and two of them (MP and MR) also decrease MCP-1 and TNF-α secretion. However, no anti-inflammatory effects were observed on 7KC- and (7KC + LPS)-treated cells. Altogether, these data bring new evidences on the potential benefits (especially antioxidant and cytoprotective properties) of Algerian mint on human health. Full article

(This article belongs to the Special Issue Lipids and Lipid Peroxidation Products in the Pathogenesis of Age-Related Diseases)

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16 pages, 2188 KiB

Open AccessArticle

Redox Regulation of Monodehydroascorbate Reductase by Thioredoxin y in Plastids Revealed in the Context of Water Stress

by Hélène Vanacker, Marjorie Guichard, Anne-Sophie Bohrer and Emmanuelle Issakidis-Bourguet

Antioxidants 2018, 7(12), 183; https://doi.org/10.3390/antiox7120183 - 6 Dec 2018

Cited by 38 | Viewed by 4240

Abstract

Thioredoxins (TRXs) are key players within the complex response network of plants to environmental constraints. Here, the physiological implication of the plastidial y-type TRXs in Arabidopsis drought tolerance was examined. We previously showed that TRXs y1 and y2 have antioxidant functions, and here, [...] Read more.

Thioredoxins (TRXs) are key players within the complex response network of plants to environmental constraints. Here, the physiological implication of the plastidial y-type TRXs in Arabidopsis drought tolerance was examined. We previously showed that TRXs y1 and y2 have antioxidant functions, and here, the corresponding single and double mutant plants were studied in the context of water deprivation. TRX y mutant plants showed reduced stress tolerance in comparison with wild-type (WT) plants that correlated with an increase in their global protein oxidation levels. Furthermore, at the level of the main antioxidant metabolites, while glutathione pool size and redox state were similarly affected by drought stress in WT and trxy1y2 plants, ascorbate (AsA) became more quickly and strongly oxidized in mutant leaves. Monodehydroascorbate (MDA) is the primary product of AsA oxidation and NAD(P)H-MDA reductase (MDHAR) ensures its reduction. We found that the extractable leaf NADPH-dependent MDHAR activity was strongly activated by TRX y2. Moreover, activity of recombinant plastid Arabidopsis MDHAR isoform (MDHAR6) was specifically increased by reduced TRX y, and not by other plastidial TRXs. Overall, these results reveal a new function for y-type TRXs and highlight their role as major antioxidants in plastids and their importance in plant stress tolerance. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)

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17 pages, 913 KiB

Open AccessReview

Involvement of Glutaredoxin and Thioredoxin Systems in the Nitrogen-Fixing Symbiosis between Legumes and Rhizobia

by Geneviève Alloing, Karine Mandon, Eric Boncompagni, Françoise Montrichard and Pierre Frendo

Antioxidants 2018, 7(12), 182; https://doi.org/10.3390/antiox7120182 - 5 Dec 2018

Cited by 20 | Viewed by 5574

Abstract

Leguminous plants can form a symbiotic relationship with Rhizobium bacteria, during which plants provide bacteria with carbohydrates and an environment appropriate to their metabolism, in return for fixed atmospheric nitrogen. The symbiotic interaction leads to the formation of a new organ, the root [...] Read more.

Leguminous plants can form a symbiotic relationship with Rhizobium bacteria, during which plants provide bacteria with carbohydrates and an environment appropriate to their metabolism, in return for fixed atmospheric nitrogen. The symbiotic interaction leads to the formation of a new organ, the root nodule, where a coordinated differentiation of plant cells and bacteria occurs. The establishment and functioning of nitrogen-fixing symbiosis involves a redox control important for both the plant-bacteria crosstalk and the regulation of nodule metabolism. In this review, we discuss the involvement of thioredoxin and glutaredoxin systems in the two symbiotic partners during symbiosis. The crucial role of glutathione in redox balance and S-metabolism is presented. We also highlight the specific role of some thioredoxin and glutaredoxin systems in bacterial differentiation. Transcriptomics data concerning genes encoding components and targets of thioredoxin and glutaredoxin systems in connection with the developmental step of the nodule are also considered in the model system Medicago truncatula–Sinorhizobium meliloti. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)

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13 pages, 1189 KiB

Open AccessArticle

Identification of Small Peptides that Inhibit NADPH Oxidase (Nox2) Activation

by Aron B. Fisher, Chandra Dodia and Sheldon I. Feinstein

Antioxidants 2018, 7(12), 181; https://doi.org/10.3390/antiox7120181 - 5 Dec 2018

Cited by 11 | Viewed by 3741

Abstract

Nicotinamide adenine phosphate (NADPH) oxidase type 2 (Nox2), a major source of reactive oxygen species in lungs, plays an important role in tissue damage associated with acute inflammatory diseases. The phospholipase A₂ (PLA₂) activity of peroxiredoxin 6 (Prdx6), called aiPLA [...] Read more.

Nicotinamide adenine phosphate (NADPH) oxidase type 2 (Nox2), a major source of reactive oxygen species in lungs, plays an important role in tissue damage associated with acute inflammatory diseases. The phospholipase A₂ (PLA₂) activity of peroxiredoxin 6 (Prdx6), called aiPLA₂, is required for Nox2 activation through its role in the cellular generation of Rac, a key cytosolic component of the activation cascade. Lung surfactant protein A (SP-A) binds to Prdx6, inhibits its aiPLA₂ activity, and prevents activation of Nox2. Based on protein docking software, we previously identified a 16 amino acid (aa) peptide derived from rat SP-A as the Prdx6 binding motif. We now identify the minimal effective sequences of rat/mouse and human SP-A as 9-aa sequences that we have called PLA₂-inhibitory peptide (PIP).These sequences are PIP-1, rat/mouse; PIP-2, human; and PIP-3, a hybrid of PIPs 1&2. aiPLA₂ activity in vitro was inhibited by 50% with ~7–10 µg PIP/µg Prdx6. Inhibition of the aiPLA₂ activity and Nox2 activation of lungs in vivo was similar for intratracheal (IT) and intravenous (IV) administration of PIP-2, but required its incorporation into liposomes as a delivery vehicle; tissue ½ time for decrease of the in vivo inhibition of aiPLA₂ activity after PIP-2 administration was ~50 h. These properties suggest that PIP-2 could be an effective therapeutic agent to prevent tissue injury associated with lung inflammation. Full article

(This article belongs to the Special Issue Peroxiredoxin 6 as a Unique Member of the Peroxiredoxin Family)

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12 pages, 1701 KiB

Open AccessArticle

Regulation of Oxidative Stress in Corneal Endothelial Cells by Prdx6

by Matthew Lovatt, Khadijah Adnan, Gary S. L. Peh and Jodhbir S. Mehta

Antioxidants 2018, 7(12), 180; https://doi.org/10.3390/antiox7120180 - 4 Dec 2018

Cited by 15 | Viewed by 4541

Abstract

The inner layer of the cornea, the corneal endothelium, is post-mitotic and unable to regenerate if damaged. The corneal endothelium is one of the most transplanted tissues in the body. Fuchs’ endothelial corneal dystrophy (FECD) is the leading indication for corneal endothelial transplantation. [...] Read more.

The inner layer of the cornea, the corneal endothelium, is post-mitotic and unable to regenerate if damaged. The corneal endothelium is one of the most transplanted tissues in the body. Fuchs’ endothelial corneal dystrophy (FECD) is the leading indication for corneal endothelial transplantation. FECD is thought to be an age-dependent disorder, with a major component related to oxidative stress. Prdx6 is an antioxidant with particular affinity for repairing peroxidised cell membranes. To address the role of Prdx6 in corneal endothelial cells, we used a combination of biochemical and functional studies. Our data reveal that Prdx6 is expressed at unusually high levels at the plasma membrane of corneal endothelial cells. RNAi-mediated knockdown of Prdx6 revealed a role for Prdx6 in lipid peroxidation. Furthermore, following induction of oxidative stress with menadione, Prdx6-deficient cells had defective mitochondrial membrane potential and were more sensitive to cell death. These data reveal that Prdx6 is compartmentalised in corneal endothelial cells and has multiple functions to preserve cellular integrity. Full article

(This article belongs to the Special Issue Peroxiredoxin 6 as a Unique Member of the Peroxiredoxin Family)

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17 pages, 1663 KiB

Open AccessReview

The Role of Cystinosin in the Intermediary Thiol Metabolism and Redox Homeostasis in Kidney Proximal Tubular Cells

by Rodolfo Sumayao, Jr., Philip Newsholme and Tara McMorrow

Antioxidants 2018, 7(12), 179; https://doi.org/10.3390/antiox7120179 - 3 Dec 2018

Cited by 21 | Viewed by 5135

Abstract

Cystinosin is a lysosomal transmembrane protein which facilitates transport of the disulphide amino acid cystine (CySS) from the lysosomes of the cell. This protein is encoded by the CTNS gene which is defective in the lysosomal storage disorder, cystinosis. Because of the apparent [...] Read more.

Cystinosin is a lysosomal transmembrane protein which facilitates transport of the disulphide amino acid cystine (CySS) from the lysosomes of the cell. This protein is encoded by the CTNS gene which is defective in the lysosomal storage disorder, cystinosis. Because of the apparent involvement of cystinosin in the intermediary thiol metabolism, its discovery has fuelled investigations into its role in modulating cellular redox homeostasis. The kidney proximal tubular cells (PTCs) have become the focus of various studies on cystinosin since the protein is highly expressed in these cells and kidney proximal tubular transport dysfunction is the foremost clinical manifestation of cystinosis. The lysosomal CySS pool is a major source of cytosolic cysteine (Cys), the limiting amino acid for the synthesis of an important antioxidant glutathione (GSH) via the γ-glutamyl cycle. Therefore, loss of cystinosin function is presumed to lead to cytosolic deficit of Cys which may impair GSH synthesis. However, studies using in vitro models lacking cystinosin yielded inconsistent results and failed to establish the mechanistic role of cystinosin in modulating GSH synthesis and redox homeostasis. Because of the complexity of the metabolic micro- and macro-environment in vivo, using in vitro models alone may not be able to capture the complete sequence of biochemical and physiological events that occur as a consequence of loss of cystinosin function. The coexistence of pathways for the overall handling and disposition of GSH, the modulation of CTNS gene by intracellular redox status and the existence of a non-canonical isoform of cystinosin may constitute possible rescue mechanisms in vivo to remediate redox perturbations in renal PTCs. Importantly, the mitochondria seem to play a critical role in orchestrating redox imbalances initiated by cystinosin dysfunction. Non-invasive techniques such as in vivo magnetic resonance imaging with the aid of systems biology approaches may provide invaluable mechanistic insights into the role of cystinosin in the essential intermediary thiol metabolism and in the overall regulation cellular redox homeostasis. Full article

(This article belongs to the Special Issue Thiol Redox Systems in Health and Disease)

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14 pages, 1689 KiB

Open AccessArticle

Effect of Extract and Ellagic Acid from Geranium schiedeanum on the Antioxidant Defense System in An Induced-Necrosis Model

by Nancy Vargas-Mendoza, Miguel Vázquez-Velasco, Laura González-Torres, Juana Benedí, Francisco José Sánchez-Muniz, Jose Antonio Morales-González, Osmar Antonio Jaramillo-Morales, Carmen Valadez-Vega and Mirandeli Bautista

Antioxidants 2018, 7(12), 178; https://doi.org/10.3390/antiox7120178 - 30 Nov 2018

Cited by 4 | Viewed by 4411

Abstract

Geranium schiedeanum has been used in traditional therapies as an antiseptic, antipyretic, and as analgesic. The present study was designed to evaluate the pretreatment with G. schiedeanum total extract (GS) and its active metabolites on stimulating the endogenous antioxidant defense system (EADS): catalase [...] Read more.

Geranium schiedeanum has been used in traditional therapies as an antiseptic, antipyretic, and as analgesic. The present study was designed to evaluate the pretreatment with G. schiedeanum total extract (GS) and its active metabolites on stimulating the endogenous antioxidant defense system (EADS): catalase (Cat), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione reduction index (RI GSH/GSSG) in rat liver treated with a sublethal dose (6.6 mmol/Kg) of thioacetamide (TAA) in order to probe the capacity of GS and the active compounds to reduce liver injury. This was assessed by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (BILT) in rats pretreated or not with TAA, and pretreated or not with GS and its metabolites. The results showed that GS was able to induce the production of EADS enzymes, increasing redox index GSH/GSSG at 24 and 48 h after intoxication, and both the extract and the ellagic acid exhibited a significant reduction of hepatic damage markers. Our data confirmed the hepatoprotective effect of GS and its metabolites, like ellagic acid, support the possible use of this extract in the treatment of liver injury. Full article

(This article belongs to the Special Issue Antioxidants in Oxidative Stress Diseases)

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16 pages, 2952 KiB

Open AccessReview

Piecing Together How Peroxiredoxins Maintain Genomic Stability

by James D. West, Trevor J. Roston, Joseph B. David, Kristin M. Allan and Matthew A. Loberg

Antioxidants 2018, 7(12), 177; https://doi.org/10.3390/antiox7120177 - 28 Nov 2018

Cited by 12 | Viewed by 5227

Abstract

Peroxiredoxins, a highly conserved family of thiol oxidoreductases, play a key role in oxidant detoxification by partnering with the thioredoxin system to protect against oxidative stress. In addition to their peroxidase activity, certain types of peroxiredoxins possess other biochemical activities, including assistance in [...] Read more.

Peroxiredoxins, a highly conserved family of thiol oxidoreductases, play a key role in oxidant detoxification by partnering with the thioredoxin system to protect against oxidative stress. In addition to their peroxidase activity, certain types of peroxiredoxins possess other biochemical activities, including assistance in preventing protein aggregation upon exposure to high levels of oxidants (molecular chaperone activity), and the transduction of redox signals to downstream proteins (redox switch activity). Mice lacking the peroxiredoxin Prdx1 exhibit an increased incidence of tumor formation, whereas baker’s yeast (Saccharomyces cerevisiae) lacking the orthologous peroxiredoxin Tsa1 exhibit a mutator phenotype. Collectively, these findings suggest a potential link between peroxiredoxins, control of genomic stability, and cancer etiology. Here, we examine the potential mechanisms through which Tsa1 lowers mutation rates, taking into account its diverse biochemical roles in oxidant defense, protein homeostasis, and redox signaling as well as its interplay with thioredoxin and thioredoxin substrates, including ribonucleotide reductase. More work is needed to clarify the nuanced mechanism(s) through which this highly conserved peroxidase influences genome stability, and to determine if this mechanism is similar across a range of species. Full article

(This article belongs to the Special Issue The Role of Peroxiredoxins in Cancer)

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13 pages, 2152 KiB

Open AccessArticle

Analysis of Protein Oxidative Modifications in Follicular Fluid from Fertile Women: Natural Versus Stimulated Cycles

by Irantzu Pérez-Ruiz, Susana Meijide, María-Luisa Hérnandez, Rosaura Navarro, Zaloa Larreategui, Marcos Ferrando, María-Begoña Ruiz-Larrea and José-Ignacio Ruiz-Sanz

Antioxidants 2018, 7(12), 176; https://doi.org/10.3390/antiox7120176 - 27 Nov 2018

Cited by 4 | Viewed by 4479

Abstract

Oxidative stress is associated with obstetric complications during ovarian hyperstimulation in women undergoing in vitro fertilization. The follicular fluid contains high levels of proteins, which are the main targets of free radicals. The aim of this work was to determine specific biomarkers of [...] Read more.

Oxidative stress is associated with obstetric complications during ovarian hyperstimulation in women undergoing in vitro fertilization. The follicular fluid contains high levels of proteins, which are the main targets of free radicals. The aim of this work was to determine specific biomarkers of non-enzymatic oxidative modifications of proteins from follicular fluid in vivo, and the effect of ovarian stimulation with gonadotropins on these biomarkers. For this purpose, 27 fertile women underwent both a natural and a stimulated cycle. The biomarkers, glutamic semialdehyde (GSA), aminoadipic semialdehyde (AASA), N^ε-(carboxymethyl)lysine (CML), and N^ε-(carboxyethyl)lysine (CEL), were measured by gas-liquid chromatography coupled to mass spectrometry. Results showed that follicular fluid contained products of protein modifications by direct metal-catalyzed oxidation (GSA and AASA), glycoxidation (CML and CEL), and lipoxidation (CML). GSA was the most abundant biomarker (91.5%). The levels of CML amounted to 6% of the total lesions and were higher than AASA (1.3%) and CEL (1.2%). In the natural cycle, CEL was significantly lower (p < 0.05) than in the stimulated cycle, suggesting that natural cycles are more protected against protein glycoxidation. These findings are the basis for further research to elucidate the possible relevance of this follicular biomarker of advanced glycation end product in fertility programs. Full article

(This article belongs to the Special Issue Oxidative Stress Biomarkers in Cardiovascular Risk and Disease)

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10 pages, 1316 KiB

Open AccessArticle

Enrichment and Assessment of the Contributions of the Major Polyphenols to the Total Antioxidant Activity of Onion Extracts: A Fractionation by Flash Chromatography Approach

by Mohammad B. Hossain, Justine Lebelle, Rares Birsan and Dilip K. Rai

Antioxidants 2018, 7(12), 175; https://doi.org/10.3390/antiox7120175 - 27 Nov 2018

Cited by 15 | Viewed by 5537

Abstract

The present study extensively fractionated crude red onion extract in order to identify the polyphenols which contributed most in the total antioxidant capacity of the onion extract using a flash chromatography system. The flash separations produced 70 fractions which were tested for their [...] Read more.

The present study extensively fractionated crude red onion extract in order to identify the polyphenols which contributed most in the total antioxidant capacity of the onion extract using a flash chromatography system. The flash separations produced 70 fractions which were tested for their total phenol content, total flavonoid content, and antioxidant capacities as measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Out of these 70 fractions, four fractions which were representatives of the four major peaks of the flash chromatograms, were further analysed for their constituent polyphenols using liquid chromatography tandem mass spectrometry (LC-MS/MS). The main contributor of onion antioxidant capacity is quercetin glycoside followed by quercetin aglycone although quercetin aglycone had higher antioxidant capacity than its glycosidic counterparts. High abundance of quercetin glycosides such as quercetin-3,4′-diglucoside and quercetin-4′-glucoside had compensated for their relatively low antioxidant capacities. A Higher degree of glycosylation resulted in lower antioxidant capacity. The fractionation approach also contributed in enrichment of the onion antioxidant polyphenols. A >9 folds enrichment was possible by discarding the early fractions (fractions 1–15) which contained the main bulk of the extracts, predominantly sugars. Full article

(This article belongs to the Special Issue Synthetic Antioxidants: Health Benefits, Hazards and Alternatives)

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12 pages, 3134 KiB

Open AccessArticle

Study of the Selectivity and Bioactivity of Polyphenols Using Infrared Assisted Extraction from Apricot Pomace Compared to Conventional Methods

by Dina Cheaib, Nada El Darra, Hiba N. Rajha, Iman El-Ghazzawi, Youssef Mouneimne, Adla Jammoul, Richard G. Maroun and Nicolas Louka

Antioxidants 2018, 7(12), 174; https://doi.org/10.3390/antiox7120174 - 27 Nov 2018

Cited by 32 | Viewed by 5336

Abstract

The valorization of industrial food byproducts by means of environment-friendly extraction methods is becoming a major interest because of its environmental and economic values. In this study, the efficiency of many technologies, such as ultrasounds (US), microwaves (MW), and infrared (IR), was compared, [...] Read more.

The valorization of industrial food byproducts by means of environment-friendly extraction methods is becoming a major interest because of its environmental and economic values. In this study, the efficiency of many technologies, such as ultrasounds (US), microwaves (MW), and infrared (IR), was compared, in terms of polyphenol yield and bioactivity from apricot pomace. IR was the most effective method with the highest polyphenol (10 mg GAE/g DM), flavonoid (6 mg CE/g DM), and tannin (3.6 mg/L) yields. In terms of efficacy, IR was followed by MW, US, then solid-liquid (S/L) extraction. IR extract from apricot pomace exhibited the highest inhibitory activity against all the studied gram-positive strains (Methicillin Resistant Staphylococcus aureus, Staphylococcus aureus, Methicillin-resistant Staphylococcus epidermidis, and Staphylococcus epidermidis) and a one gram-negative strain (Escherichia coli). Moreover, IR extracts had by far the highest antiradical activity (AC) (40%) followed by MW (31%), US (28%), and then S/L (15%). High-performance liquid chromatography (HPLC) permitted the identification and quantification of rutin in all extracts; whereas catechin was detected in those of IR (3.1 μg/g DM), MW (2.1 μg/g DM), and US (1.5 μg/g DM). Epicatechin was exclusively found in IR extract (4 μg/g DM), suggesting the selectivity of IR towards this compound. Scanning electron microscopy (SEM) revealed that the IR technique induced the highest cellular and structural damage in apricot pomace, which could explain the effectiveness of this technology. Full article

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9 pages, 418 KiB

Open AccessReview

Peroxiredoxin 6: The Protector of Male Fertility

by Cristian O’Flaherty

Antioxidants 2018, 7(12), 173; https://doi.org/10.3390/antiox7120173 - 24 Nov 2018

Cited by 40 | Viewed by 5238

Abstract

The spermatozoon is a terminal cell with the unique purpose of delivering the paternal genome to the oocyte during fertilization. Once spermatozoa enter into the female reproductive tract, they count on only the antioxidant protection that they received during spermatogenesis and epididymal maturation. [...] Read more.

The spermatozoon is a terminal cell with the unique purpose of delivering the paternal genome to the oocyte during fertilization. Once spermatozoa enter into the female reproductive tract, they count on only the antioxidant protection that they received during spermatogenesis and epididymal maturation. Peroxiredoxins (PRDXs), particularly PRDX6, are important players in the antioxidant protection and regulation of reactive oxygen species (ROS) levels in spermatozoa. PRDX6, through its peroxidase and calcium-independent phospholipase A₂ activities, plays a major role in the regulation of ROS to maintain viability and motility and allow the spermatozoon to achieve fertilizing ability during the complex process of capacitation. The absence of PRDX6 is sufficient to promote abnormal reproductive outcomes in mice that resemble what we observe in infertile men. Indeed, Prdx6^−/− spermatozoa display low motility and severe DNA damage, which is translated into reduced ability to fertilize oocytes in vitro or produce a low number of pups compared to wild-type controls. This review focuses on the role of PRDX6 as the primary antioxidant enzyme that protects the spermatozoon from oxidative-stress-associated damages to protect the paternal genome and assure fertility. Full article

(This article belongs to the Special Issue Peroxiredoxin 6 as a Unique Member of the Peroxiredoxin Family)

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12 pages, 238 KiB

Open AccessReview

The Role of Peroxiredoxin 6 in Cell Signaling

by José A. Arevalo and José Pablo Vázquez-Medina

Antioxidants 2018, 7(12), 172; https://doi.org/10.3390/antiox7120172 - 24 Nov 2018

Cited by 71 | Viewed by 6608

Abstract

Peroxiredoxin 6 (Prdx6, 1-cys peroxiredoxin) is a unique member of the peroxiredoxin family that, in contrast to other mammalian peroxiredoxins, lacks a resolving cysteine and uses glutathione and π glutathione S-transferase to complete its catalytic cycle. Prdx6 is also the only peroxiredoxin capable [...] Read more.

Peroxiredoxin 6 (Prdx6, 1-cys peroxiredoxin) is a unique member of the peroxiredoxin family that, in contrast to other mammalian peroxiredoxins, lacks a resolving cysteine and uses glutathione and π glutathione S-transferase to complete its catalytic cycle. Prdx6 is also the only peroxiredoxin capable of reducing phospholipid hydroperoxides through its glutathione peroxidase (Gpx) activity. In addition to its peroxidase activity, Prdx6 expresses acidic calcium-independent phospholipase A₂ (aiPLA₂) and lysophosphatidylcholine acyl transferase (LPCAT) activities in separate catalytic sites. Prdx6 plays crucial roles in lung phospholipid metabolism, lipid peroxidation repair, and inflammatory signaling. Here, we review how the distinct activities of Prdx6 are regulated during physiological and pathological conditions, in addition to the role of Prdx6 in cellular signaling and disease. Full article

(This article belongs to the Special Issue Peroxiredoxin 6 as a Unique Member of the Peroxiredoxin Family)

17 pages, 2278 KiB

Open AccessArticle

Crystal Structure of Chloroplastic Thioredoxin f2 from Chlamydomonas reinhardtii Reveals Distinct Surface Properties

by Stéphane D. Lemaire, Daniele Tedesco, Pierre Crozet, Laure Michelet, Simona Fermani, Mirko Zaffagnini and Julien Henri

Antioxidants 2018, 7(12), 171; https://doi.org/10.3390/antiox7120171 - 23 Nov 2018

Cited by 16 | Viewed by 4821

Abstract

Protein disulfide reduction by thioredoxins (TRXs) controls the conformation of enzyme active sites and their multimeric complex formation. TRXs are small oxidoreductases that are broadly conserved in all living organisms. In photosynthetic eukaryotes, TRXs form a large multigenic family, and they have been [...] Read more.

Protein disulfide reduction by thioredoxins (TRXs) controls the conformation of enzyme active sites and their multimeric complex formation. TRXs are small oxidoreductases that are broadly conserved in all living organisms. In photosynthetic eukaryotes, TRXs form a large multigenic family, and they have been classified in different types: f, m, x, y, and z types are chloroplastic, while o and h types are located in mitochondria and cytosol. In the model unicellular alga Chlamydomonas reinhardtii, the TRX family contains seven types, with f- and h-types represented by two isozymes. Type-f TRXs interact specifically with targets in the chloroplast, controlling photosynthetic carbon fixation by the Calvin–Benson cycle. We solved the crystal structures of TRX f2 and TRX h1 from C. reinhardtii. The systematic comparison of their atomic features revealed a specific conserved electropositive crown around the active site of TRX f, complementary to the electronegative surface of their targets. We postulate that this surface provides specificity to each type of TRX. Full article

(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)

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17 pages, 676 KiB

Open AccessReview

Biological Relevance of Extra Virgin Olive Oil Polyphenols Metabolites

by Gabriele Serreli and Monica Deiana

Antioxidants 2018, 7(12), 170; https://doi.org/10.3390/antiox7120170 - 22 Nov 2018

Cited by 134 | Viewed by 9726

Abstract

Extra virgin olive oil (EVOO) polyphenols beneficial effects have widely been debated throughout the last three decades, with greater attention to hydroxytyrosol and tyrosol, which are by far the most studied. The main concern about the evaluation of EVOO phenols activities in vitro [...] Read more.

Extra virgin olive oil (EVOO) polyphenols beneficial effects have widely been debated throughout the last three decades, with greater attention to hydroxytyrosol and tyrosol, which are by far the most studied. The main concern about the evaluation of EVOO phenols activities in vitro and in vivo is that the absorption and metabolism of these compounds once ingested lead to the production of different metabolites in the human body. EVOO phenols in the ingested forms are less concentrated in human tissues than their glucuronide, sulfate and methyl metabolites; on the other hand, metabolites may undergo deconjugation before entering the cells and thus act as free forms or may be reformed inside the cells so acting as conjugated forms. In most in vitro studies the presence of methyl/sulfate/glucuronide functional groups does not seem to inhibit biological activity. Parent compounds and metabolites have been shown to reach tissue concentrations useful to exert beneficial effects others than antioxidant and scavenging properties, by modulating intracellular signaling and improving cellular response to oxidative stress and pro-inflammatory stimuli. This review aims to give an overview on the reported evidence of the positive effects exerted by the main EVOO polyphenols metabolites in comparison with the parent compounds. Full article

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Antioxidants, Volume 7, Issue 12 (December 2018) – 28 articles

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