Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities

Antioxid Redox Signal. 2011 Oct 1;15(7):1957-97. doi: 10.1089/ars.2010.3586. Epub 2011 Apr 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / therapy
  • Cell Death
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / therapy
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Gene Expression
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Glutathione Peroxidase / antagonists & inhibitors
  • Glutathione Peroxidase / chemistry
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism*
  • Humans
  • Molecular Sequence Data
  • Neoplasms / etiology
  • Neoplasms / genetics*
  • Neoplasms / therapy
  • Oxidation-Reduction
  • Oxidative Stress
  • Polymorphism, Genetic
  • Protein Conformation
  • Reactive Oxygen Species / metabolism
  • Risk Factors
  • Selenocysteine / chemistry
  • Selenocysteine / metabolism

Substances

  • Enzyme Inhibitors
  • Reactive Oxygen Species
  • Selenocysteine
  • glutathione peroxidase GPX1
  • Glutathione Peroxidase