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This Article Full Text Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: 297/2/H735    most recent 01164.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yu, Z. Articles by Yang, H.-T. PubMed PubMed Citation Articles by Yu, Z. Articles by Yang, H.-T.

Calcium/calmodulin-dependent protein kinase II mediates cardioprotection of intermittent hypoxia against ischemic-reperfusion-induced cardiac dysfunction

¹Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and ²Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai, China

Submitted 1 November 2008 ; accepted in final form 9 June 2009

Intermittent high-altitude (IHA) hypoxia-induced cardioprotection against ischemia-reperfusion (I/R) injury is associated with the preservation of sarcoplasmic reticulum (SR) function. Although Ca²⁺/calmodulin (CaM)-dependent protein kinase II (CaMKII) and phosphatase are known to modulate the function of cardiac SR under physiological conditions, the status of SR CaMKII and phosphatase during I/R in the hearts from IHA hypoxic rats is unknown. In the present study, we determined SR and cytosolic CaMKII activity during preischemia and I/R (30 min/30 min) in perfused hearts from normoxic and IHA hypoxic rats. The left ventricular contractile recovery, SR CaMKII activity as well as phosphorylation of phospholamban at Thr¹⁷, and Ca²⁺/CaM-dependent SR Ca²⁺-uptake activity were depressed in the I/R hearts from normoxic rats, whereas these changes were prevented in the hearts from IHA hypoxic rats. Such beneficial effects of IHA hypoxia were lost by treating the hearts with a specific CaMKII inhibitor, KN-93. I/R also depressed cytosolic CaMKII and SR phosphatase activity, but these alterations remained unchanged in IHA hypoxic group. Furthermore, we found that the autophosphorylation at Thr²⁸⁷, which confers Ca²⁺/CaM-independent activity, was not altered by I/R in both groups. These findings indicate that preservation of SR CaMKII activity plays an important role in the IHA hypoxia-induced cardioprotection against I/R injury via maintaining SR Ca²⁺-uptake activity.

cardiac sarcoplasmic reticulum; phospholamban phosphorylation residue; sarcoplasmic reticulum calcium pump adenosinetriphosphatase; phosphatase; cardiac contractile function