Deficiency of methionine sulfoxide reductase A causes cellular dysfunction and mitochondrial damage in cardiac myocytes under physical and oxidative stresses.
Biochem Biophys Res Commun
; 402(4): 608-13, 2010 Nov 26.
Article
in En
| MEDLINE
| ID: mdl-20971073
ABSTRACT
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 (2Hz), 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 2Hz 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 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stress, Mechanical
/
Oxidative Stress
/
Myocytes, Cardiac
/
Methionine Sulfoxide Reductases
/
Mitochondria, Heart
/
Myocardial Contraction
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2010
Document type:
Article
Affiliation country:
United States