Heat shock protein 27 regulates oxidative stress-induced apoptosis in cardiomyocytes: mechanisms via reactive oxygen species generation and Akt activation.
BACKGROUND
Increased reactive oxygen species (ROS) formation, which in turn promotes cardiomyocytes apoptosis, is associated with the pathogenesis and progression of various cardiac diseases such as ischemia and heart failure. Recent studies have shown that over expression of heat shock protein 27 (Hsp27) confers resistance to cardiac ischemia/reperfusion injury. However, not much is known about the regulation of myocyte survival by Hsp27.


METHODS
The rat cardiac cell line H9c2, with a stable overexpression of Hsp27, was established, with empty vector transfected H9c2 cells as controls. Following the cells challenged by Hydrogen Peroxide (H2O2), lactate dehydrogenase (LDH) release, apoptosis, intracellular ROS, cell morphology, mitochondrial transmembrane potential and the activation of serine/threonine kinase Akt were determined.


RESULTS
Along with marked suppression of H2O2-induced injury by Hsp27 overexpression in H9c2 cells, ROS generation and the loss of mitochondrial membrane potential were also significantly depressed. Furthermore, augmented Akt activation was observed in Hsp27 overexpressed H9c2 cells following H2O2 exposure.


CONCLUSIONS
Hsp27 inhibits oxidative stress-induced H9c2 damage and inhibition of ROS generation and the augmentation of Akt activation may be involved in the protective signaling.
Liu
Li
L
Department of Geriatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Zhang
Xiao-jin
XJ
Jiang
Su-rong
SR
Ding
Zheng-nian
ZN
Ding
Guo-xian
GX
Huang
Jun
J
Cheng
Yun-lin
YL
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D018832:Molecular Chaperones; D032383:Myocytes, Cardiac / Q000473:pathology*; D009363:Neoplasm Proteins / Q000502:physiology*; D018384:Oxidative Stress; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt