Methionine sulfoxide reductase A protects neuronal cells against brief hypoxia/reoxygenation

Olena Yermolaieva, Rong Xu, Carrie Schinstock, Nathan Brot, Herbert Weissbach, Stefan H. Heinemann, Toshinori Hoshi

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Hypoxia/reoxygenation induces cellular injury by promoting oxidative stress. Reversible oxidation of methionine in proteins involving the enzyme peptide methionine sulfoxide reductase type A (MSRA) is postulated to serve a general antioxidant role. Therefore, we examined whether overexpression of MSRA protected cells from hypoxia/reoxygenation injury. Brief hypoxia increased the intracellular reactive oxygen species (ROS) level in PC12 cells and promoted apoptotic cell death. Adenovirus-mediated overexpression of MSRA significantly diminished the hypoxia-induced increase in ROS and facilitated cell survival. Measurements of the membrane potentials of intact mitochondria in PC12 cells and of isolated rat liver mitochondria showed that hypoxia induced depolarization of the mitochondrial membrane. The results demonstrate that MSRA plays a protective role against hypoxia/reoxygenation-induced cell injury and suggest the therapeutic potential of MSRA in ischemic heart and brain disease.

Original languageEnglish
Pages (from-to)1159-1164
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number5
DOIs
StatePublished - 3 Feb 2004

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Methionine Sulfoxide Reductases
PC12 Cells
Reactive Oxygen Species
Wounds and Injuries
Cell Hypoxia
Liver Mitochondrion
Mitochondrial Membranes
Brain Diseases
Adenoviridae
Methionine
Membrane Potentials
Myocardial Ischemia
Cell Survival
Mitochondria
Oxidative Stress
Cell Death
Antioxidants
Hypoxia
Enzymes

Cite this

Yermolaieva, Olena ; Xu, Rong ; Schinstock, Carrie ; Brot, Nathan ; Weissbach, Herbert ; Heinemann, Stefan H. ; Hoshi, Toshinori. / Methionine sulfoxide reductase A protects neuronal cells against brief hypoxia/reoxygenation. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 5. pp. 1159-1164.
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Methionine sulfoxide reductase A protects neuronal cells against brief hypoxia/reoxygenation. / Yermolaieva, Olena; Xu, Rong; Schinstock, Carrie; Brot, Nathan; Weissbach, Herbert; Heinemann, Stefan H.; Hoshi, Toshinori.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 5, 03.02.2004, p. 1159-1164.

Research output: Contribution to journalArticle

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T1 - Methionine sulfoxide reductase A protects neuronal cells against brief hypoxia/reoxygenation

AU - Yermolaieva, Olena

AU - Xu, Rong

AU - Schinstock, Carrie

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AU - Weissbach, Herbert

AU - Heinemann, Stefan H.

AU - Hoshi, Toshinori

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AB - Hypoxia/reoxygenation induces cellular injury by promoting oxidative stress. Reversible oxidation of methionine in proteins involving the enzyme peptide methionine sulfoxide reductase type A (MSRA) is postulated to serve a general antioxidant role. Therefore, we examined whether overexpression of MSRA protected cells from hypoxia/reoxygenation injury. Brief hypoxia increased the intracellular reactive oxygen species (ROS) level in PC12 cells and promoted apoptotic cell death. Adenovirus-mediated overexpression of MSRA significantly diminished the hypoxia-induced increase in ROS and facilitated cell survival. Measurements of the membrane potentials of intact mitochondria in PC12 cells and of isolated rat liver mitochondria showed that hypoxia induced depolarization of the mitochondrial membrane. The results demonstrate that MSRA plays a protective role against hypoxia/reoxygenation-induced cell injury and suggest the therapeutic potential of MSRA in ischemic heart and brain disease.

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