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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/H1633    most recent 01227.2008v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Whittaker, R. Articles by Glembotski, C. C. Search for Related Content PubMed PubMed Citation Articles by Whittaker, R. Articles by Glembotski, C. C.

Kinetics of the translocation and phosphorylation of B-crystallin in mouse heart mitochondria during ex vivo ischemia

San Diego State University Heart Institute and Department of Biology, San Diego State University, San Diego, California

Submitted 22 November 2008 ; accepted in final form 21 February 2009

B-crystallin (BC) is a small heat shock protein expressed at high levels in the myocardium where it protects from ischemia-reperfusion damage. Ischemia-reperfusion activates p38 MAP kinase, leading to the phosphorylation of BC on serine 59 (P-BC-S59), enhancing its ability to protect myocardial cells from damage. In the heart, ischemia-reperfusion also causes the translocation of BC from the cytosol to other cellular locations, one of which was recently shown to be mitochondria. However, it is not known whether BC translocates to mitochondria during ischemia-reperfusion, nor is it known whether BC phosphorylation takes place before or after translocation. In the present study, analyses of mitochondrial fractions isolated from mouse hearts subjected to various times of ex vivo ischemia-reperfusion showed that BC translocation to mitochondria was maximal after 20 min of ischemia and then declined steadily during reperfusion. Phosphorylation of mitochondrial BC was maximal after 30 min of ischemia, suggesting that at least in part it occurred after BC association with mitochondria. Consistent with this was the finding that translocation of activated p38 to mitochondria was maximal after only 10 min of ischemia. The overexpression of BC-AAE, which mimics BC phosphorylated on serine 59, has been shown to stabilize mitochondrial membrane potential and to inhibit apoptosis. In the present study, infection of neonatal rat cardiac myocytes with adenovirus-encoded BC-AAE decreased peroxide-induced mitochondrial cytochrome c release. These results suggest that during ischemia BC translocates to mitochondria, where it is phosphorylated and contributes to modulating mitochondrial damage upon reperfusion.

cardiac myocyte; p38 mitogen-activated protein kinase