Cited by 1,280Selenium in Biological SystemsRedox biology and oxidative stressOrganoselenium and organotellurium chemistry

Glutathione Peroxidase-1 in Health and Disease: From Molecular Mechanisms to Therapeutic Opportunities

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Lubos, Edith, Loscalzo, Joseph, Handy, Diane E.·2011·Antioxidants & Redox Signaling

Abstract

Reactive oxygen species, such as superoxide and hydrogen peroxide, are generated in all cells by mitochondrial and enzymatic sources. Left unchecked, these reactive species can cause oxidative damage to DNA, proteins, and membrane lipids. Glutathione peroxidase-1 (GPx-1) is an intracellular antioxidant enzyme that enzymatically reduces hydrogen peroxide to water to limit its harmful effects. Certain reactive oxygen species, such as hydrogen peroxide, are also essential for growth factor-mediated signal transduction, mitochondrial function, and maintenance of normal thiol redox-balance. Thus, by limiting hydrogen peroxide accumulation, GPx-1 also modulates these processes. This review explores the molecular mechanisms involved in regulating the expression and function of GPx-1, with an emphasis on the role of GPx-1 in modulating cellular oxidant stress and redox-mediated responses. As a selenocysteine-containing enzyme, GPx-1 expression is subject to unique forms of regulation involving the trace mineral selenium and selenocysteine incorporation during translation. In addition, GPx-1 has been implicated in the development and prevention of many common and complex diseases, including cancer and cardiovascular disease. This review discusses the role of GPx-1 in these diseases and speculates on potential future therapies to harness the beneficial effects of this ubiquitous antioxidant enzyme. Antioxid. Redox Signal. 15, 1957–1997.

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Crossref · 10.1089/ars.2010.3586

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Authors
Lubos, E., Loscalzo, J., & Handy, D. E.
Affiliations
  • Johannes Gutenberg University Mainz (DE)
  • Brigham and Women's Hospital (US)
Corresponding author
Handy, Diane E.
Venue
Antioxidants & Redox Signaling
Published
2011-10
Volume
15
Issue
7
Pages
1957-1997
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W1963668163
Cited by
1,280
References
421
Citations by year
2026: 85 · 2025: 126 · 2024: 146 · 2023: 136 · 2022: 138 · 2021: 131 · 2020: 107 · 2019: 94 · 2018: 61 · 2017: 56 · 2016: 55 · 2015: 40 · 2014: 45 · 2013: 24 · 2012: 27
FWCI
2.15
Type
journal article
Language
en
Open access
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Deutsche Forschungsgemeinschaft
  • National Institutes of Health (HL 61795, HL081587)
  • National Heart, Lung, and Blood Institute (HL61795, HL 089734, HL081587, P01HL081587, R21HL089734, R01HL061795)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Organoselenium and organotellurium chemistry
Keywords
glutathione peroxidase 1, reactive oxygen species, hydrogen peroxide, oxidative stress, antioxidant enzymes, selenocysteine incorporation, selenium, mitochondrial function, cancer, cardiovascular disease
MeSH terms
Glutathione Peroxidase GPX1, Amino Acid Sequence, Animals, Cardiovascular Diseases, Diabetes Mellitus, Enzyme Inhibitors, Gene Expression Regulation, Glutathione Peroxidase, Humans, Molecular Sequence Data, Neoplasms, Oxidation-Reduction, Polymorphism, Genetic, Protein Conformation, Risk Factors, Gene Expression, Cell Death, Selenocysteine, Reactive Oxygen Species, Oxidative Stress, Genetic Predisposition to Disease

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