A Dynamic Pathway for Calcium-Independent Activation of CaMKII by Methionine Oxidation

Jeffrey R Erickson; 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

doi:10.1016/j.cell.2008.02.048

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A Dynamic Pathway for Calcium-Independent Activation of CaMKII by Methionine Oxidation

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A Dynamic Pathway for Calcium-Independent Activation of CaMKII by Methionine Oxidation

Jeffrey R Erickson, 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, …

Cell (Cambridge), Vol.133(3), pp.462-474

2008

DOI: 10.1016/j.cell.2008.02.048

PMCID: PMC2435269

PMID: 18455987

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Abstract

Calcium/calmodulin (Ca 2+/CaM)-dependent protein kinase II (CaMKII) couples increases in cellular Ca 2+ to fundamental responses in excitable cells. CaMKII was identified over 20 years ago by activation dependence on Ca 2+/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 Ca 2+/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.

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Title: Subtitle: A Dynamic Pathway for Calcium-Independent Activation of CaMKII by Methionine Oxidation
Creators: Jeffrey R Erickson - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242-1109, USA
Mei-ling A Joiner - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242-1109, USA
Xiaoqun Guan - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242-1109, USA
William Kutschke - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242-1109, USA
Jinying Yang - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242-1109, USA
Carmine V Oddis - Department of Internal Medicine, Vanderbilt University, Nashville, TN 37232-0615, USA
Ryan K Bartlett - Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232-0615, USA
John S Lowe - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242-1109, USA
Susan E O'Donnell - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242-1109, USA
Nukhet Aykin-Burns - Department of Radiation Oncology, Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA, 52242-1109, USA
Matthew C Zimmerman - Department of Radiation Oncology, Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA, 52242-1109, USA
Kathy Zimmerman - Department of Veterans Affairs Medical Center, Iowa City, IA 52242-1109, USA
Amy-Joan L Ham - Department of Biochemistry, Vanderbilt University, Nashville, TN 37232-0615, USA
Robert M Weiss - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242-1109, USA
Douglas R Spitz - Department of Radiation Oncology, Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA, 52242-1109, USA
Madeline A Shea - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242-1109, USA
Roger J Colbran - Department of Biochemistry, Vanderbilt University, Nashville, TN 37232-0615, USA
Peter J Mohler - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242-1109, USA
Mark E Anderson - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242-1109, USA
Resource Type: Journal article
Publication Details: Cell (Cambridge), Vol.133(3), pp.462-474
Publisher: Elsevier Inc
DOI: 10.1016/j.cell.2008.02.048
PMID: 18455987
PMCID: PMC2435269
ISSN: 0092-8674
eISSN: 1097-4172
Language: English
Date published: 2008
Academic Unit: Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Cardiovascular Medicine; Biology; Radiation Oncology; Anesthesia; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984024565702771

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