title: Novel functional role of heat shock protein 90 in protein kinase C-mediated ischemic postconditioning.
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).
  
  
  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.
authors.affiliation: Department of Geriatric Cardiology, First Affiliated Hospital, Guang Xi Medical University, Nanning, China; Department of Cardiology, First Affiliated Hospital, Guang Xi Medical University, Nanning, China. Electronic address: guoqiang_zhong@sina.cn.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Zhong
authors.affiliation: Department of Geriatric Cardiology, First Affiliated Hospital, Guang Xi Medical University, Nanning, China.
authors.forename: Rong-Hui
authors.initials: RH
authors.lastname: Tu
authors.affiliation: Department of Geriatric Cardiology, First Affiliated Hospital, Guang Xi Medical University, Nanning, China.
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Zeng
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Guang Xi Medical University, Nanning, China.
authors.forename: Qing-Jie
authors.initials: QJ
authors.lastname: Li
authors.affiliation: Department of Geriatric Cardiology, First Affiliated Hospital, Guang Xi Medical University, Nanning, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Guang Xi Medical University, Nanning, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Geriatric Cardiology, First Affiliated Hospital, Guang Xi Medical University, Nanning, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Guang Xi Medical University, Nanning, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D016227:Benzoquinones; D015153:Blotting, Western; D018834:Chaperonin 60 / Q000378:metabolism*; D052279:Creatine Kinase, MB Form / Q000097:blood; D057775:Ischemic Postconditioning; D007770:L-Lactate Dehydrogenase / Q000097:blood; D047029:Lactams, Macrocyclic; D008297:Male; D008928:Mitochondria / Q000648:ultrastructure; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000648:ultrastructure; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D018834:Chaperonin 60; D047029:Lactams, Macrocyclic; D051028:bcl-2-Associated X Protein; D007770:L-Lactate Dehydrogenase; D051744:Protein Kinase C-epsilon; D052279:Creatine Kinase, MB Form; C001277:geldanamycin
keywords: Heart; Heat shock protein; Ischemic postconditioning; Protein kinase C; Rat