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The Role of Glutathione Metabolism in Health and Disease
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The Role of Glutathione Metabolism in Health and Disease

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

Deadline for manuscript submissions: closed (25 June 2024) | Viewed by 4811

Special Issue Editor

Dr. Marlena Brzozowa-Zasada

E-Mail Website
Guest Editor
Department of Histology and Cell Pathology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 40-055 Katowice, Poland
Interests: colon cancer; gastric cancer; Notch signaling pathway; glutathione in cancer; antioxidant enzymes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glutathione (GSH) is essential for several antioxidant processes and appears to be the most important non-enzymatic antioxidant in cells. For example, it acts as a regulator of the cellular redox state to protect cells from damage caused by lipid peroxides, reactive oxygen and nitrogen species, and xenobiotics. GSH has also been shown to participate in key signalling pathways and to regulate, e.g., proliferation or apoptosis. One of the most important roles of GSH is its involvement in the regeneration of enzymatic and non-enzymatic antioxidants. Cancer initiation, progression, and response to treatment have been linked to molecular alterations in the GSH antioxidant system and disruption of GSH homeostasis. It is also worth noting that in healthy cells it is essential for removing and detoxifying carcinogens, whereas elevated GSH levels in cancer cells have been linked to tumour progression and increased resistance to chemotherapeutic drugs.

Therefore, a better understanding of the role of GSH in health and diseases, including cancer, especially at the molecular level, may improve prognosis and treatment response. For this Special Issue, we invite manuscripts on the role of GSH (and enzymes which are connected with GSH activity) in healthy cells and pathological tissues.

Dr. Marlena Brzozowa-Zasada
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glutathione metabolism
  • glutathione activity
  • cancer
  • reactive oxygen species (ROS)

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Published Papers (3 papers)

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Research

18 pages, 3539 KiB  
Article
Lipid Peroxidation Regulators GPX4 and FSP1 as Prognostic Markers and Therapeutic Targets in Advanced Gastric Cancer
by Kazuhiro Tamura, Yoshinobu Tomita, Takumi Kanazawa, Hajime Shinohara, Masayoshi Sakano, Sachiko Ishibashi, Masumi Ikeda, Mayumi Kinoshita, Junko Minami, Kurara Yamamoto, Yuki Kato, Asuka Furukawa, Shigeo Haruki, Masanori Tokunaga, Yusuke Kinugasa, Morito Kurata, Masanobu Kitagawa, Kenichi Ohashi and Kouhei Yamamoto
Int. J. Mol. Sci. 2024, 25(17), 9203; https://doi.org/10.3390/ijms25179203 - 24 Aug 2024
Viewed by 1118
Abstract
Gastric cancer is one of the most common cancers worldwide, and new therapeutic strategies are urgently needed. Ferroptosis is an intracellular iron-dependent cell death induced by the accumulation of lipid peroxidation, a mechanism different from conventional apoptosis and necrosis. Therefore, induction of ferroptosis [...] Read more.
Gastric cancer is one of the most common cancers worldwide, and new therapeutic strategies are urgently needed. Ferroptosis is an intracellular iron-dependent cell death induced by the accumulation of lipid peroxidation, a mechanism different from conventional apoptosis and necrosis. Therefore, induction of ferroptosis is expected to be a new therapeutic strategy. Glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) have been identified as the major inhibitors of ferroptosis. Herein, we performed immunohistochemistry for GPX4, FSP1, and 4-HNE using tissues from patients with gastric cancer and investigated the relationship between these factors and prognosis. Patients with high GPX4 expression or high GPX4 expression and low 4-HNE accumulation tended to have a poor prognosis (p = 0.036, 0.023), whereas those with low FSP1 expression and high 4-HNE accumulation had a good prognosis (p = 0.033). The synergistic induction of cell death by inhibiting GPX4 and FSP1 in vitro was also observed, indicating that the cell death was non-apoptotic. Our results indicate that the expression and accumulation of lipid peroxidation-related factors play an important role in the clinicopathological significance of gastric cancer and that novel therapeutic strategies targeting GPX4 and FSP1 may be effective in treating patients with gastric cancer who have poor prognosis. Full article
(This article belongs to the Special Issue The Role of Glutathione Metabolism in Health and Disease)
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23 pages, 9050 KiB  
Article
A Prognostic Activity of Glutaredoxin 1 Protein (Grx1) in Colon Cancer
by Marlena Brzozowa-Zasada, Adam Piecuch, Karolina Bajdak-Rusinek, Karolina Gołąbek, Marek Michalski, Natalia Matysiak and Zenon Czuba
Int. J. Mol. Sci. 2024, 25(2), 1007; https://doi.org/10.3390/ijms25021007 - 13 Jan 2024
Cited by 1 | Viewed by 1494
Abstract
Glutaredoxin 1 (Grx1) is an essential enzyme that regulates redox signal transduction and repairs protein oxidation by reversing S-glutathionylation, an oxidative modification of protein cysteine residues. Grx1 removes glutathione from proteins to restore their reduced state (protein-SH) and regulate protein-SSG levels in redox [...] Read more.
Glutaredoxin 1 (Grx1) is an essential enzyme that regulates redox signal transduction and repairs protein oxidation by reversing S-glutathionylation, an oxidative modification of protein cysteine residues. Grx1 removes glutathione from proteins to restore their reduced state (protein-SH) and regulate protein-SSG levels in redox signaling networks. Thus, it can exert an influence on the development of cancer. To further investigate this problem, we performed an analysis of Grx1 expression in colon adenocarcinoma samples from the Polish population of patients with primary colon adenocarcinoma (stages I and II of colon cancer) and those with regional lymph node metastasis (stage III of colon cancer). Our study revealed a significant correlation between the expression of Grx1 protein through immunohistochemical analysis and various clinical characteristics of patients, such as histological grade, depth of invasion, angioinvasion, staging, regional lymph node invasion, and PCNA expression. It was found that almost 88% of patients with stage I had high levels of Grx1 expression, while only 1% of patients with stage III exhibited high levels of Grx1 protein expression. Furthermore, the study discovered that high levels of Grx1 expression were present in samples of colon mucosa without any pathological changes. These results were supported by in vitro analysis conducted on colorectal cancer cell lines that corresponded to stages I, II, and III of colorectal cancer, using qRT-PCR and Western blot. Full article
(This article belongs to the Special Issue The Role of Glutathione Metabolism in Health and Disease)
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16 pages, 3512 KiB  
Article
Immunohistochemical Expression of Glutathione Peroxidase-2 (Gpx-2) and Its Clinical Relevance in Colon Adenocarcinoma Patients
by Marlena Brzozowa-Zasada, Angela Ianaro, Adam Piecuch, Marek Michalski, Natalia Matysiak and Katarzyna Stęplewska
Int. J. Mol. Sci. 2023, 24(19), 14650; https://doi.org/10.3390/ijms241914650 - 27 Sep 2023
Cited by 7 | Viewed by 1600
Abstract
Glutathione peroxidase 2 (Gpx-2) is a selenoenzyme with antioxidant capabilities that may play a role in cancer development. Hence, we investigated the immunohistochemical expression of Gpx-2 protein in colon adenocarcinoma samples derived from patients with colon adenocarcinoma who did not receive any form [...] Read more.
Glutathione peroxidase 2 (Gpx-2) is a selenoenzyme with antioxidant capabilities that may play a role in cancer development. Hence, we investigated the immunohistochemical expression of Gpx-2 protein in colon adenocarcinoma samples derived from patients with colon adenocarcinoma who did not receive any form of treatment prior to the surgical procedure. The associations between the immunohistochemical expression of Gpx-2 and clinical parameters were analysed using the Chi2 test and Fisher’s exact test. A Kaplan–Meier analysis and the log-rank test were used to verify the relationship between the intensity of Gpx-2 expression and the 5-year survival rate of patients. In total, 101 (80.80%) samples had strong Gpx-2 protein expression and 24 (19.20%) samples were characterized with low expression. The high expression of Gpx-2 was correlated with the histological grade of the tumour (p < 0.001), PCNA immunohistochemical expression (p < 0.001), depth of invasion (p = 0.001) and angioinvasion (p < 0.001). We can conclude that high expression of Gpx-2 is correlated with reduced survival of colon adenocarcinoma patients (log-rank, p < 0.001). Full article
(This article belongs to the Special Issue The Role of Glutathione Metabolism in Health and Disease)
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