title: Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities.
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.
authors.affiliation: Department of Medicine II, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Edith
authors.initials: E
authors.lastname: Lubos
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
authors.forename: Diane E
authors.initials: DE
authors.lastname: Handy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics / Q000628:therapy; D016923:Cell Death; D003920:Diabetes Mellitus / Q000209:etiology / Q000235:genetics / Q000628:therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015870:Gene Expression; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D017279:Selenocysteine / Q000737:chemistry / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D017279:Selenocysteine; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human