Deficiency of methionine sulfoxide reductase A causes cellular dysfunction and mitochondrial damage in cardiac myocytes under physical and oxidative stresses
- College of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431 (United States)
- Center for Molecular Biology and Biotechnology, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431 (United States)
Research highlights: {yields} Deficiency of MsrA in the heart renders myocardial cells more sensitive to oxidative stress. {yields} Mitochondrial damage happens in the heart lacking MsrA. {yields} More protein oxidation in myocardial cells lacking MsrA. {yields} MsrA protects the heart against oxidative stress. -- Abstract: Methionine sulfoxide reductase A (MsrA) is an enzyme that reverses oxidation of methionine in proteins. Using a MsrA gene knockout (MsrA{sup -/-}) 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{sup -/-} 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{sup -/-} cardiac myocytes. MsrA{sup -/-} cardiac myocytes also show a significant decrease in contractility after oxidative stress using H{sub 2}O{sub 2}. Corresponding changes in Ca{sup 2+} transients are observed in MsrA{sup -/-} cardiomyocytes treated with 2 Hz stimulation or with H{sub 2}O{sub 2}. Electron microscope analyses reveal a dramatic morphological change of mitochondria in MsrA{sup -/-} mouse hearts. Further biochemical measurements indicate that protein oxidation levels in MsrA{sup -/-} mouse hearts are significantly higher than those in wild type controls. Our study demonstrates that the lack of MsrA in cardiac myocytes reduces myocardial cell's capability against stress stimulations resulting in a cellular dysfunction in the heart.
- OSTI ID:
- 22202901
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 402, Issue 4; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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