@article{a89e36ac8b5140b78b1ca5439fbc1290,
title = "A Dynamic Pathway for Calcium-Independent Activation of CaMKII by Methionine Oxidation",
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.",
keywords = "HUMDISEASE, SIGNALING",
author = "Erickson, {Jeffrey R.} and Joiner, {Mei ling A.} and Xiaoqun Guan and William Kutschke and Jinying Yang and Oddis, {Carmine V.} and Bartlett, {Ryan K.} and Lowe, {John S.} and O'Donnell, {Susan E.} and Nukhet Aykin-Burns and Zimmerman, {Matthew C.} and Kathy Zimmerman and Ham, {Amy Joan L.} and Weiss, {Robert M.} and Spitz, {Douglas R.} and Shea, {Madeline A.} and Colbran, {Roger J.} and Mohler, {Peter J.} and Anderson, {Mark E.}",
note = "Funding Information: The authors wish to acknowledge discussions with Dr. Botond Bonfi, Dr. Trudy Burns, Dr. Johannes Hell, Dr. David Murhammer, Dr. Stefan Strack, and Dr. Michael Welsh (University of Iowa) and technical contributions of Chantal Allamargot (University of Iowa Central Microscopy Research Facility). The authors also wish to acknowledge the graphic design contributions of Shawn Roach (University of Iowa). Mice lacking the MsrA gene were generously provided by Dr. Earl Stadtman of NIH (Bethesda, MD, USA). This work was funded by NIH R01 HL 079031, R01 HL 62494, and R01 HL 70250 (M.E.A.); NIH R01 HL084583 and R01 HL083422 and Pew Scholars Trust (P.J.M.); NIH R01 GM57001 (M.A.S.); NIH RR017369 (R.M.W.); UI CVC Interdisciplinary Research Fellowship (J.R.E.); UI Center for Biocatalysis and Bioprocessing Fellowship (S.E.O.); and the University of Iowa Research Foundation. ",
year = "2008",
month = may,
day = "2",
doi = "10.1016/j.cell.2008.02.048",
language = "English (US)",
volume = "133",
pages = "462--474",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}