Deficiency of methionine sulfoxide reductase A causes cellular dysfunction and mitochondrial damage in cardiac myocytes under physical and oxidative stresses

作者：Nan Changlong; Li Yuejin; Jean Charles Pierre Yves; Chen Guozhen; Kreymerman Alexander; Prentice Howard; Weis**ach Herbert; Huang Xupei^*

来源：Biochemical and Biophysical Research Communications, 2010, 402(4): 608-613.

DOI：10.1016/j.bbrc.2010.10.064

• Methionine sulfoxide reductase
• Mitochondria
• Cardiac contractility
• Protein oxidation
• Knockout mice

Methionine sulfoxide reductase A (MsrA) is an enzyme that reverses oxidation of methionine in proteins Using a MsrA gene knockout (MsrA(-/-)) mouse model we have investigated the role of MsrA in the heart Our data indicate that cellular contractility and cardiac function are not significantly changed in MsrA(-/-) mice if the hearts are not stressed However the cellular contractility when stressed using a higher stimulation frequency (2 Hz) is significantly reduced in MsrA(-/-) cardiac myocytes MsrA(-/-) cardiac myocytes also show a significant decrease in contractility after oxidative stress using H(2)O(2) Corresponding changes in Ca(2+) transients are observed in MsrA(-/-) cardiomyocytes treated with 2 Hz stimulation or with H(2)O(2) Electron microscope analyses reveal a dramatic morphological change of mitochondria in MsrA(-/-) mouse hearts Further biochemical measurements indicate that protein oxidation levels in MsrA-/- mouse hearts are significantly higher than those in wild type controls Our study demonstrat

• 出版日期2010-11-26