MsrA protects cardiac myocytes against hypoxia/reoxygenation induced cell death.
Reactive oxygen species (ROS) are critical in tissue responses to ischemia-reperfusion. The enzyme methionine sulfoxide reductase-A (MsrA) is capable of protecting cells against oxidative damage by reversing damage to proteins caused by methionine oxidation or by decreasing ROS through a scavenger mechanism. The current study employed adenovirus mediated over-expression of MsrA in primary neonatal rat cardiac myocytes to determine the effect of this enzyme in protecting against hypoxia/reoxygenation in this tissue. Cells were transduced with MsrA encoding adenovirus and subjected to hypoxia/reoxygenation. Apoptotic cell death was decreased by greater than 45% in cells over-expressing MsrA relative to cells transduced with a control virus. Likewise total cell death as determined by levels of LDH release was dramatically decreased by MsrA over-expression. These observations indicate that MsrA is protective against hypoxia/reoxygenation stress in cardiac myocytes and point to MsrA as an important therapeutic target for ischemic heart disease.
Prentice
H M
HM
Florida Atlantic University, College of Biomedical Science, 777 Glades Road, Boca Raton, FL 33431, USA.
Moench
I A
IA
Rickaway
Z T
ZT
Dougherty
C J
CJ
Webster
K A
KA
Weissbach
H
H
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002316:Cardiotonic Agents / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002316:Cardiotonic Agents; D017382:Reactive Oxygen Species; D010088:Oxidoreductases; C488525:MsrA protein, rat