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Adaptation to Hypoxia: A Chimera?

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (25 September 2019) | Viewed by 51481

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Guest Editor
Centre Hospitalier Universitaire Vaudois Lausanne, Lausanne, Switzerland
Interests: chronic hypoxia; acute myocardial infarction; cardioprotection; hypoxic pulmonary hypertension; ischemia reperfusion injury; cardiac regeneration; cardiotoxicity; echocardiography; animal models
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Dear Colleagues,

The Chimera was, according to Greek mythology, a monstrous fire-breathing hybrid creature of Lycia in Asia Minor, composed of the parts of more than one animal. Hence, the term "chimera" has come to describe anything composed of very disparate parts, or perceived as wildly imaginative, implausible, or dazzling (adapted from Wikipedia).

A world-relevant clinical and environment issue that affects millions of people, hypoxia, i.e., the insufficient supply of oxygen with respect to demand, constitutes an important source of social and economic distress. Despite hypoxia representing a potentially lethal condition, the human body possesses reserves that enable the recruitment of defense mechanisms to grant survival during relatively acute episodes. Clearly, however, when sustained or chronic, hypoxia is predicted to request a greater effort to balance its harmful effects, despite a longer time allowed to recruit gene-based and proteomic compensatory mechanisms. Chronic exposure to stressors, however, implies the concept of adaptation, or the “modification of an organism or its parts that makes it more fit for existence under the conditions of its environment: a heritable physical or behavioral trait that serves a specific function and improves an organism's fitness or survival” (Merriam-Webster Dictionary). Because at least some of the biological systems that constitute complex living matter have limited regenerative capacity, such as the cerebral and cardiopulmonary systems, the concept of adaptation is, therefore, particularly relevant, but several unanswered undeveloped questions, arise:

  1. How can we assess the onset of adaptation? In other words, which physiological (e.g., blunted erythropoiesis, control of alkalemia due to excess ventilation, recovery of body’s homeostasis), molecular (e.g., normalization of NO stores, recruitment of hypoxia-sensitive genes and proteins), pathological (e.g., weight at birth, resistance against cardiopulmonary diseases, integrity of the cerebral function) best represent a target of adaptation?
  2. Does adaptation invest the whole body or can some organs/functions become better or faster adapted than others? This question may be linked to other important sub-questions: (1) Why are some populations better adapted than others, for example, Tibetan vs. South American dwellers? (2) How do Ethiopians, Kirgiz, long-term inhabitants of the Antarctica rank with respect to the mentioned Tibetan and South Americans dwellers? (3) Why do comparable degrees of hypoxia in some categories of patients lead to deleterious consequences, for example, blue babies and patients with COPD or pulmonary hypertension?
  3. Sometimes, high-altitude people opt to reside at lower altitudes. Can adaptation work in a reverse mode by enabling altitude-adapted people to survive relatively oxygen-rich atmospheres?
  4. Is adaptation always a positive factor, or are there instances where adaptation, or better maladaptation, might lead to deleterious patterns?
  5. Are factors such as the degree of activity, intermittent exposure to different oxygen levels, and life habits critical to enabling better and faster adaptation? Is there a role for the hypoxia-induced oxidative stress in these patterns?
  6. Is the classical HIF-1a pathway sufficient to explain the complexity of the responses to chronic hypoxia and to enable adaptive patterns?
  7. Are appropriate biomarkers available to assess the degree of adaptation, or the lack of adaptation to hypoxia?

We believe that answering these questions may enable us to understand whether humans, who underwent a genetical selection as a low-altitude population, may ever be able to adapt to either environmental or pathological hypoxia, or if hypoxia adaptation is and will remain a chimera.

Prof. Dr. Michele Samaja
Dr. Giuseppina Milano
Guest Editors

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Keywords

  • adaptation
  • chronic hypoxia
  • intermittent hypoxia
  • hyperoxia
  • hypoxia mimetics
  • hypoxia antagonists
  • oxygen sensing
  • hypoxia-inducible factors
  • adaptation
  • high altitude
  • tumor microenvironment
  • pulmonary dysfunction
  • cardiovascular disease
  • apoptosis

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Published Papers (12 papers)

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Editorial

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4 pages, 182 KiB  
Editorial
Adaptation to Hypoxia: A Chimera?
by Michele Samaja and Giuseppina Milano
Int. J. Mol. Sci. 2020, 21(4), 1527; https://doi.org/10.3390/ijms21041527 - 24 Feb 2020
Cited by 8 | Viewed by 3134
Abstract
The Chimera was, according to Greek mythology, a monstrous fire-breathing hybrid creature of Lycia in Asia Minor, composed of the parts of more than one animal [...] Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)

Research

Jump to: Editorial, Review, Other

17 pages, 2519 KiB  
Article
Hypoxic-Inflammatory Responses under Acute Hypoxia: In Vitro Experiments and Prospective Observational Expedition Trial
by Tobias Kammerer, Valentina Faihs, Nikolai Hulde, Manfred Stangl, Florian Brettner, Markus Rehm, Mareike Horstmann, Julia Kröpfl, Christina Spengler, Simone Kreth and Simon Schäfer
Int. J. Mol. Sci. 2020, 21(3), 1034; https://doi.org/10.3390/ijms21031034 - 4 Feb 2020
Cited by 27 | Viewed by 3917
Abstract
Induction of hypoxia-inducible-factor-1α (HIF-1α) pathway and HIF-target genes allow adaptation to hypoxia and are associated with reduced incidence of acute mountain sickness (AMS). Little is known about HIF-pathways in conjunction with inflammation or exercise stimuli under acute hypobaric hypoxia in non-acclimatized individuals. We [...] Read more.
Induction of hypoxia-inducible-factor-1α (HIF-1α) pathway and HIF-target genes allow adaptation to hypoxia and are associated with reduced incidence of acute mountain sickness (AMS). Little is known about HIF-pathways in conjunction with inflammation or exercise stimuli under acute hypobaric hypoxia in non-acclimatized individuals. We therefore tested the hypotheses that (1) both hypoxic and inflammatory stimuli induce hypoxic-inflammatory signaling pathways in vitro, (2) similar results are seen in vivo under hypobaric hypoxia, and (3) induction of HIF-dependent genes is associated with AMS in 11 volunteers. In vitro, peripheral blood mononuclear cells (PBMCs) were incubated under hypoxic (10%/5% O2) or inflammatory (CD3/CD28) conditions. In vivo, Interleukin 1β (IL-1β), C-X-C Chemokine receptor type 4 (CXCR-4), and C-C Chemokine receptor type 2 (CCR-2) mRNA expression, cytokines and receptors were analyzed under normoxia (520 m above sea level (a.s.l.)), hypobaric hypoxia (3883 m a.s.l.) before/after exercise, and after 24 h under hypobaric hypoxia. In vitro, isolated hypoxic (p = 0.004) or inflammatory (p = 0.006) stimuli induced IL-1β mRNA expression. CCR-2 mRNA expression increased under hypoxia (p = 0.005); CXCR-4 mRNA expression remained unchanged. In vivo, cytokines, receptors, and IL-1β, CCR-2 and CXCR-4 mRNA expression increased under hypobaric hypoxia after 24 h (all p ≤ 0.05). Of note, proinflammatory IL-1β and CXCR-4 mRNA expression changes were associated with symptoms of AMS. Thus, hypoxic-inflammatory pathways are differentially regulated, as combined hypoxic and exercise stimulus was stronger in vivo than isolated hypoxic or inflammatory stimulation in vitro. Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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20 pages, 3120 KiB  
Article
Intermittent Hypoxic Conditioning Alleviates Post-Traumatic Stress Disorder-Induced Damage and Dysfunction of Rat Visceral Organs and Brain
by Eugenia B. Manukhina, Vadim E. Tseilikman, Marina N. Karpenko, Nina S. Pestereva, Olga B. Tseilikman, Maria V. Komelkova, Marina V. Kondashevskaya, Anna V. Goryacheva, Maxim S. Lapshin, Pavel O. Platkovskii, Alexey P. Sarapultsev, Anatoly V. Alliluev and H. Fred Downey
Int. J. Mol. Sci. 2020, 21(1), 345; https://doi.org/10.3390/ijms21010345 - 5 Jan 2020
Cited by 20 | Viewed by 4880
Abstract
Posttraumatic stress disorder (PTSD) causes mental and somatic diseases. Intermittent hypoxic conditioning (IHC) has cardio-, vaso-, and neuroprotective effects and alleviates experimental PTSD. IHC’s ability to alleviate harmful PTSD effects on rat heart, liver, and brain was examined. PTSD was induced by 10-day [...] Read more.
Posttraumatic stress disorder (PTSD) causes mental and somatic diseases. Intermittent hypoxic conditioning (IHC) has cardio-, vaso-, and neuroprotective effects and alleviates experimental PTSD. IHC’s ability to alleviate harmful PTSD effects on rat heart, liver, and brain was examined. PTSD was induced by 10-day exposure to cat urine scent (PTSD rats). Some rats were then adapted to 14-day IHC (PTSD+IHC rats), while PTSD and untreated control rats were cage rested. PTSD rats had a higher anxiety index (AI, X-maze test), than control or PTSD+IHC rats. This higher AI was associated with reduced glycogen content and histological signs of metabolic and hypoxic damage and of impaired contractility. The livers of PTSD rats had reduced glycogen content. Liver and blood alanine and aspartate aminotransferase activities of PTSD rats were significantly increased. PTSD rats had increased norepinephrine concentration and decreased monoamine oxidase A activity in cerebral cortex. The PTSD-induced elevation of carbonylated proteins and lipid peroxidation products in these organs reflects oxidative stress, a known cause of organ pathology. IHC alleviated PTSD-induced metabolic and structural injury and reduced oxidative stress. Therefore, IHC is a promising preventive treatment for PTSD-related morphological and functional damage to organs, due, in part, to IHC’s reduction of oxidative stress. Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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12 pages, 2270 KiB  
Article
Oxidative Stress Markers to Investigate the Effects of Hyperoxia in Anesthesia
by Sara Ottolenghi, Federico Maria Rubino, Giovanni Sabbatini, Silvia Coppola, Alice Veronese, Davide Chiumello and Rita Paroni
Int. J. Mol. Sci. 2019, 20(21), 5492; https://doi.org/10.3390/ijms20215492 - 4 Nov 2019
Cited by 33 | Viewed by 4506
Abstract
Oxygen (O2) is commonly used in clinical practice to prevent or treat hypoxia, but if used in excess (hyperoxia), it may act as toxic. O2 toxicity arises from the enhanced formation of Reactive Oxygen Species (ROS) that exceed the antioxidant [...] Read more.
Oxygen (O2) is commonly used in clinical practice to prevent or treat hypoxia, but if used in excess (hyperoxia), it may act as toxic. O2 toxicity arises from the enhanced formation of Reactive Oxygen Species (ROS) that exceed the antioxidant defenses and generate oxidative stress. In this study, we aimed at assessing whether an elevated fraction of inspired oxygen (FiO2) during and after general anesthesia may contribute to the unbalancing of the pro-oxidant/antioxidant equilibrium. We measured five oxidative stress biomarkers in blood samples from patients undergoing elective abdominal surgery, randomly assigned to FiO2 = 0.40 vs. 0.80: hydroperoxides, antioxidants, nitrates and nitrites (NOx), malondialdehyde (MDA), and glutathionyl hemoglobin (HbSSG). The MDA concentration was significantly higher 24 h after surgery, and the body antioxidant defense lower, in the FiO2 = 0.80 group with respect to both the FiO2 = 0.40 group and the baseline values (p ≤ 0.05, Student’s t-test). HbSSG in red blood cells was also higher in the FiO2 = 0.80 group at the end of the surgery. NOx was higher in the FiO2 = 0.80 group than the FiO2 = 0.40 group at t = 2 h after surgery. MDA, the main end product of the peroxidation of polyunsaturated fatty acids directly influenced by FiO2, may represent the best marker to assess the pro-oxidant/antioxidant equilibrium after surgery. Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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0 pages, 1897 KiB  
Article
RETRACTED: Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer’s Disease in Patients with Mild Cognitive Impairment: A Pilot Study
by Zoya O. Serebrovska, Tetiana V. Serebrovska, Viktor A. Kholin, Lesya V. Tumanovska, Angela M. Shysh, Denis A. Pashevin, Sergii V. Goncharov, Dmytro Stroy, Oksana N. Grib, Valeriy B. Shatylo, Natalia Yu. Bachinskaya, Egor Egorov, Lei Xi and Victor E. Dosenko
Int. J. Mol. Sci. 2019, 20(21), 5405; https://doi.org/10.3390/ijms20215405 - 30 Oct 2019
Cited by 69 | Viewed by 7759 | Retraction
Abstract
Alzheimer’s disease (AD) affects not only the central nervous system, but also peripheral blood cells including neutrophils and platelets, which actively participate in pathogenesis of AD through a vicious cycle between platelets aggregation and production of excessive amyloid beta (Aβ). Platelets adhesion on [...] Read more.
Alzheimer’s disease (AD) affects not only the central nervous system, but also peripheral blood cells including neutrophils and platelets, which actively participate in pathogenesis of AD through a vicious cycle between platelets aggregation and production of excessive amyloid beta (Aβ). Platelets adhesion on amyloid plaques also increases the risk of cerebral microcirculation disorders. Moreover, activated platelets release soluble adhesion molecules that cause migration, adhesion/activation of neutrophils and formation of neutrophil extracellular traps (NETs), which may damage blood brain barrier and destroy brain parenchyma. The present study examined the effects of intermittent hypoxic-hyperoxic training (IHHT) on elderly patients with mild cognitive impairment (MCI), a precursor of AD. Twenty-one participants (age 51–74 years) were divided into three groups: Healthy Control (n = 7), MCI+Sham (n = 6), and MCI+IHHT (n = 8). IHHT was carried out five times per week for three weeks (total 15 sessions). Each IHHT session consisted of four cycles of 5-min hypoxia (12% FIO2) and 3-min hyperoxia (33% FIO2). Cognitive parameters, Aβ and amyloid precursor protein (APP) expression, microRNA 29, and long non-coding RNA in isolated platelets as well as NETs in peripheral blood were investigated. We found an initial decline in cognitive function indices in both MCI+Sham and MCI+IHHT groups and significant correlations between cognitive test scores and the levels of circulating biomarkers of AD. Whereas sham training led to no change in these parameters, IHHT resulted in the improvement in cognitive test scores, along with significant increase in APP ratio and decrease in Aβ expression and NETs formation one day after the end of three-week IHHT. Such effects on Aβ expression and NETs formation remained more pronounced one month after IHHT. In conclusion, our results from this pilot study suggested a potential utility of IHHT as a new non-pharmacological therapy to improve cognitive function in pre-AD patients and slow down the development of AD. Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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19 pages, 2199 KiB  
Article
The Fast Lane of Hypoxic Adaptation: Glucose Transport Is Modulated via A HIF-Hydroxylase-AMPK-Axis in Jejunum Epithelium
by Franziska Dengler and Gotthold Gäbel
Int. J. Mol. Sci. 2019, 20(20), 4993; https://doi.org/10.3390/ijms20204993 - 9 Oct 2019
Cited by 13 | Viewed by 3055
Abstract
The intestinal epithelium is able to adapt to varying blood flow and, thus, oxygen availability. Still, the adaptation fails under pathologic situations. A better understanding of the mechanisms underlying the epithelial adaptation to hypoxia could help to improve the therapeutic approach. We hypothesized [...] Read more.
The intestinal epithelium is able to adapt to varying blood flow and, thus, oxygen availability. Still, the adaptation fails under pathologic situations. A better understanding of the mechanisms underlying the epithelial adaptation to hypoxia could help to improve the therapeutic approach. We hypothesized that the short-term adaptation to hypoxia is mediated via AMP-activated protein kinase (AMPK) and that it is coupled to the long-term adaptation by a common regulation mechanism, the HIF-hydroxylase enzymes. Further, we hypothesized the transepithelial transport of glucose to be part of this short-term adaptation. We conducted Ussing chamber studies using isolated lagomorph jejunum epithelium and cell culture experiments with CaCo-2 cells. The epithelia and cells were incubated under 100% and 21% O2, respectively, with the panhydroxylase inhibitor dimethyloxalylglycine (DMOG) or under 1% O2. We showed an activation of AMPK under hypoxia and after incubation with DMOG by Western blot. This could be related to functional effects like an impairment of Na+-coupled glucose transport. Inhibitor studies revealed a recruitment of glucose transporter 1 under hypoxia, but not after incubation with DMOG. Summing up, we showed an influence of hydroxylase enzymes on AMPK activity and similarities between hypoxia and the effects of hydroxylase inhibition on functional changes. Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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11 pages, 1795 KiB  
Article
Radical Stress Is More Cytotoxic in the Nucleus than in Other Organelles
by Laurent M. Paardekooper, Ellen van Vroonhoven, Martin ter Beest and Geert van den Bogaart
Int. J. Mol. Sci. 2019, 20(17), 4147; https://doi.org/10.3390/ijms20174147 - 25 Aug 2019
Cited by 15 | Viewed by 4872
Abstract
Cells are exposed to reactive oxygen species (ROS) as a by-product of mitochondrial metabolism, especially under hypoxia. ROS are also enzymatically generated at the plasma membrane during inflammation. Radicals cause cellular damage leading to cell death, as they react indiscriminately with surrounding lipids, [...] Read more.
Cells are exposed to reactive oxygen species (ROS) as a by-product of mitochondrial metabolism, especially under hypoxia. ROS are also enzymatically generated at the plasma membrane during inflammation. Radicals cause cellular damage leading to cell death, as they react indiscriminately with surrounding lipids, proteins, and nucleotides. However, ROS are also important for many physiological processes, including signaling, pathogen killing and chemotaxis. The sensitivity of cells to ROS therefore likely depends on the subcellular location of ROS production, but how this affects cell viability is poorly understood. As ROS generation consumes oxygen, and hypoxia-mediated signaling upregulates expression of antioxidant transcription factor Nrf2, it is difficult to discern hypoxic from radical stress. In this study, we developed an optogenetic toolbox for organelle-specific generation of ROS using the photosensitizer protein SuperNova which produces superoxide anion upon excitation with 590 nm light. We fused SuperNova to organelle specific localization signals to induce ROS with high precision. Selective ROS production did not affect cell viability in most organelles except for the nucleus. SuperNova is a promising tool to induce locally targeted ROS production, opening up new possibilities to investigate processes and organelles that are affected by localized ROS production. Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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15 pages, 1240 KiB  
Article
Regulation of Serum Sphingolipids in Andean Children Born and Living at High Altitude (3775 m)
by Pietro Barbacini, Josefina Casas, Enrica Torretta, Daniele Capitanio, Gustavo Maccallini, Valeria Hirschler and Cecilia Gelfi
Int. J. Mol. Sci. 2019, 20(11), 2835; https://doi.org/10.3390/ijms20112835 - 11 Jun 2019
Cited by 17 | Viewed by 4540
Abstract
Recent studies on Andean children indicate a prevalence of dyslipidemia and hypertension compared to dwellers at lower altitudes, suggesting that despite similar food intake and daily activities, they undergo different metabolic adaptations. In the present study, the sphingolipid pattern was investigated in serum [...] Read more.
Recent studies on Andean children indicate a prevalence of dyslipidemia and hypertension compared to dwellers at lower altitudes, suggesting that despite similar food intake and daily activities, they undergo different metabolic adaptations. In the present study, the sphingolipid pattern was investigated in serum of 7 underweight (UW), 30 normal weight (NW), 13 overweight (OW), and 9 obese (O) Andean children by liquid chromatography-mass spectrometry (LC-MS). Results indicate that levels of Ceramides (Cers) and sphingomyelins (SMs) correlate positively with biochemical parameters (except for Cers and Vitamin D, which correlate negatively), whereas sphingosine-1-phosphate (S1P) correlates negatively. Correlation results and LC-MS data identify the axis high density lipoprotein-cholesterol (HDL-C), Cers, and S1P as related to hypoxia adaptation. Specifically UW children are characterized by increased levels of S1P compared to O and lower levels of Cers compared to NW children. Furthermore, O children show lower levels of S1P and similar levels of Cers and SMs as NW. In conclusion, our results indicate that S1P is the primary target of hypoxia adaptation in Andean children, and its levels are associated with hypoxia tolerance. Furthermore, S1P can act as marker of increased risk of metabolic syndrome and cardiac dysfunction in young Andeans living at altitude. Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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16 pages, 2298 KiB  
Article
Adaptive Changes of Glioblastoma Cells Following Exposure to Hypoxic (1% Oxygen) Tumour Microenvironment
by Ahmed Musah-Eroje and Sue Watson
Int. J. Mol. Sci. 2019, 20(9), 2091; https://doi.org/10.3390/ijms20092091 - 28 Apr 2019
Cited by 27 | Viewed by 4249
Abstract
Glioblastoma multiforme is the most aggressive and malignant primary brain tumour, with a median survival rate of between 15 to 17 months. Heterogeneous regions occur in glioblastoma as a result of oxygen gradients which ranges from 0.1% to 10% in vivo. Emerging evidence [...] Read more.
Glioblastoma multiforme is the most aggressive and malignant primary brain tumour, with a median survival rate of between 15 to 17 months. Heterogeneous regions occur in glioblastoma as a result of oxygen gradients which ranges from 0.1% to 10% in vivo. Emerging evidence suggests that tumour hypoxia leads to increased aggressiveness and chemo/radio resistance. Yet, few in vitro studies have been performed in hypoxia. Using three glioblastoma cell-lines (U87, U251, and SNB19), the adaptation of glioblastoma cells in a 1% (hypoxia) and 20% (normoxia) oxygen microenvironment on proliferation, metabolism, migration, neurosphere formation, CD133 and VEGF expression was investigated. Compared to cells maintained in normoxia (20% oxygen), glioblastoma cells adapted to 1% oxygen tension by reducing proliferation and enhancing metabolism. Both migratory tendency and neurosphere formation ability were greatly limited. In addition, hypoxic-mediated gene upregulation (CD133 and VEGF) was reversed when cells were removed from the hypoxic environment. Collectively, our results reveal that hypoxia plays a pivotal role in changing the behaviour of glioblastoma cells. We have also shown that genetic modulation can be reversed, supporting the concept of reversibility. Thus, understanding the degree of oxygen gradient in glioblastoma will be crucial in personalising treatment for glioblastoma patients. Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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20 pages, 11753 KiB  
Article
Identification and Characterization of Four Autophagy-Related Genes That Are Expressed in Response to Hypoxia in the Brain of the Oriental River Prawn (Macrobrachium nipponense)
by Shengming Sun, Ying Wu, Hongtuo Fu, Xianping Ge, Hongzheng You and Xugan Wu
Int. J. Mol. Sci. 2019, 20(8), 1856; https://doi.org/10.3390/ijms20081856 - 15 Apr 2019
Cited by 10 | Viewed by 3155
Abstract
Autophagy is a cytoprotective mechanism triggered in response to adverse environmental conditions. Herein, we investigated the autophagy process in the oriental river prawn (Macrobrachium nipponense) following hypoxia. Full-length cDNAs encoding autophagy-related genes (ATGs) ATG3, ATG4B, ATG5, and ATG9A [...] Read more.
Autophagy is a cytoprotective mechanism triggered in response to adverse environmental conditions. Herein, we investigated the autophagy process in the oriental river prawn (Macrobrachium nipponense) following hypoxia. Full-length cDNAs encoding autophagy-related genes (ATGs) ATG3, ATG4B, ATG5, and ATG9A were cloned, and transcription following hypoxia was explored in different tissues and developmental stages. The ATG3, ATG4B, ATG5, and ATG9A cDNAs include open reading frames encoding proteins of 319, 264, 268, and 828 amino acids, respectively. The four M. nipponense proteins clustered separately from vertebrate homologs in phylogenetic analysis. All four mRNAs were expressed in various tissues, with highest levels in brain and hepatopancreas. Hypoxia up-regulated all four mRNAs in a time-dependent manner. Thus, these genes may contribute to autophagy-based responses against hypoxia in M. nipponense. Biochemical analysis revealed that hypoxia stimulated anaerobic metabolism in the brain tissue. Furthermore, in situ hybridization experiments revealed that ATG4B was mainly expressed in the secretory and astrocyte cells of the brain. Silencing of ATG4B down-regulated ATG8 and decreased cell viability in juvenile prawn brains following hypoxia. Thus, autophagy is an adaptive response protecting against hypoxia in M. nipponense and possibly other crustaceans. Recombinant MnATG4B could interact with recombinant MnATG8, but the GST protein could not bind to MnATG8. These findings provide us with a better understanding of the fundamental mechanisms of autophagy in prawns. Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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Review

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18 pages, 843 KiB  
Review
Iron and Sphingolipids as Common Players of (Mal)Adaptation to Hypoxia in Pulmonary Diseases
by Sara Ottolenghi, Aida Zulueta and Anna Caretti
Int. J. Mol. Sci. 2020, 21(1), 307; https://doi.org/10.3390/ijms21010307 - 2 Jan 2020
Cited by 19 | Viewed by 5013
Abstract
Hypoxia, or lack of oxygen, can occur in both physiological (high altitude) and pathological conditions (respiratory diseases). In this narrative review, we introduce high altitude pulmonary edema (HAPE), acute respiratory distress syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), and Cystic Fibrosis (CF) as [...] Read more.
Hypoxia, or lack of oxygen, can occur in both physiological (high altitude) and pathological conditions (respiratory diseases). In this narrative review, we introduce high altitude pulmonary edema (HAPE), acute respiratory distress syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), and Cystic Fibrosis (CF) as examples of maladaptation to hypoxia, and highlight some of the potential mechanisms influencing the prognosis of the affected patients. Among the specific pathways modulated in response to hypoxia, iron metabolism has been widely explored in recent years. Recent evidence emphasizes hepcidin as highly involved in the compensatory response to hypoxia in healthy subjects. A less investigated field in the adaptation to hypoxia is the sphingolipid (SPL) metabolism, especially through Ceramide and sphingosine 1 phosphate. Both individually and in concert, iron and SPL are active players of the (mal)adaptation to physiological hypoxia, which can result in the pathological HAPE. Our aim is to identify some pathways and/or markers involved in the physiological adaptation to low atmospheric pressures (high altitudes) that could be involved in pathological adaptation to hypoxia as it occurs in pulmonary inflammatory diseases. Hepcidin, Cer, S1P, and their interplay in hypoxia are raising growing interest both as prognostic factors and therapeutical targets. Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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Other

2 pages, 143 KiB  
Retraction
RETRACTED: Serebrovska et al. Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer’s Disease in Patients with Mild Cognitive Impairment: A Pilot Study. Int. J. Mol. Sci. 2019, 20, 5405
by Zoya O. Serebrovska, Tetiana V. Serebrovska, Viktor A. Kholin, Lesya V. Tumanovska, Angela M. Shysh, Denis A. Pashevin, Sergii V. Goncharov, Dmytro Stroy, Oksana N. Grib, Valeriy B. Shatylo, Natalia Yu. Bachinskaya, Egor Egorov, Lei Xi and Victor E. Dosenko
Int. J. Mol. Sci. 2024, 25(9), 5039; https://doi.org/10.3390/ijms25095039 - 7 May 2024
Viewed by 1406
Abstract
The journal Int [...] Full article
(This article belongs to the Special Issue Adaptation to Hypoxia: A Chimera?)
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