| Literature DB >> 18455987 |
Jeffrey R Erickson1, Mei-ling A Joiner, Xiaoqun Guan, William Kutschke, Jinying Yang, Carmine V Oddis, Ryan K Bartlett, John S Lowe, Susan E O'Donnell, Nukhet Aykin-Burns, Matthew C Zimmerman, Kathy Zimmerman, Amy-Joan L Ham, Robert M Weiss, Douglas R Spitz, Madeline A Shea, Roger J Colbran, Peter J Mohler, Mark E Anderson.
Abstract
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.Entities:
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Year: 2008 PMID： 18455987 PMCID： PMC2435269 DOI： 10.1016/j.cell.2008.02.048
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582