Abstract
Background
Previous studies have shown that heat shock protein 90 (HSP90) plays a vital role
in ischemic preconditioning. The present study was designed to explore whether HSP90
might be responsible for cardioprotection in ischemic postconditioning (PostC).
Materials and methods
Rat hearts underwent 30 min of regional ischemia and 2 h of reperfusion in situ, and PostC was effected with three cycles of 30-s reperfusion and 30-s coronary artery
occlusion at the end of ischemia. Ninety rats were randomized into five groups: sham;
ischemia–reperfusion (I/R); PostC; 1 mg/kg HSP90 inhibitor geldanamycin (GA) plus
PostC (PostC + GA1); and 5 mg/kg GA plus PostC (PostC + GA5). The GA was administered
10 min before reperfusion.
Results
Compared with the I/R group, the PostC group exhibited lower infarct size (46.7 ± 3.0%
versus 27.4 ± 4.0%, respectively), release of lactate dehydrogenase and creatine kinase-MB
(2252.6 ± 350.8 versus 1713.7 ± 202.4 IU/L, 2804.3 ± 315.7 versus 1846.2 ± 238.0 IU/L, respectively), cardiomyocyte apoptosis (48.4 ± 5.6% versus 27.6 ± 3.8%, respectively), and mitochondrial damage. These beneficial effects were
accompanied by an increase in mitochondrial Bcl-2 levels and a decrease in Bax levels.
In addition, mitochondrial protein kinase Cepsilon (PKCepsilon) was relatively low
in the I/R group but significantly higher in the PostC group, whereas cytosolic PKCepsilon
was relatively high in the I/R group but significantly lower in the PostC group, suggesting
the translocation of PKCepsilon from cytosol to mitochondria during PostC. However,
blocking HSP90 function with GA inhibited the protection of PostC and PKCepsilon mitochondrial
translocation.
Conclusions
HSP90 is critical in PostC-induced cardioprotection, and its activity might be linked
to mitochondrial targeting of PKCepsilon, the activation of which results in upregulation
of its target gene, Bcl-2, and the inhibition of proapoptotic Bax in mitochondria.
Keywords
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Article info
Publication history
Published online: January 31, 2014
Accepted:
January 24,
2014
Received in revised form:
January 19,
2014
Received:
October 17,
2013
Identification
Copyright
© 2014 Published by Elsevier Inc.
