期刊
CELL
卷 133, 期 3, 页码 462-474出版社
CELL PRESS
DOI: 10.1016/j.cell.2008.02.048
关键词
-
资金
- NCRR NIH HHS [K26 RR017369, RR017369] Funding Source: Medline
- NHLBI NIH HHS [R01 HL083422, R01 HL 70250, R01 HL062494-09, R01 HL 079031, R01 HL070250-06A1, R01 HL 62494, R01 HL070250, R01 HL079031-02, R01 HL084583, R01 HL079031, R01 HL062494] Funding Source: Medline
- NIGMS NIH HHS [R01 GM57001, R01 GM057001] Funding Source: Medline
- NIMH NIH HHS [R01 MH063232, R01 MH063232-08] Funding Source: Medline
Calcium/calmodulin (Ca2+/CaM)-dependent protein kinase II (CaMKII) couples increases in cellular Ca2+ to fundamental responses in excitable cells. CaMKII was identified over 20 years ago by activation dependence on Ca2+/CaM, but recent evidence shows that CaMKII activity is also enhanced by pro-oxidant conditions. Here we show that oxidation of paired regulatory domain methionine residues sustains CaMKII activity in the absence of Ca2+/CaM. CaMKII is activated by angiotensin II (AngII)-induced oxidation, leading to apoptosis in cardiomyocytes both in vitro and in vivo. CaMKII oxidation is reversed by methionine sulfoxide reductase A (MsrA), and MsrA(-/-) mice show exaggerated CaMKII oxidation and myocardial apoptosis, impaired cardiac function, and increased mortality after myocardial infarction. Our data demonstrate a dynamic mechanism for CaMKII activation by oxidation and highlight the critical importance of oxidation-dependent CaMKII activation to AngII and ischemic myocardial apoptosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据