Increased expression of heat shock protein 90 under chemical hypoxic conditions protects cardiomyocytes against injury induced by serum and glucose deprivation

Wu,Keng; Xu,Wenming; You,Qiong; Guo,Runmin; Feng,Jianqiang; Zhang,Changran; Wu,Wen

doi:10.3892/ijmm.2012.1099

Increased expression of heat shock protein 90 under chemical hypoxic conditions protects cardiomyocytes against injury induced by serum and glucose deprivation

Authors:
- Keng Wu
- Wenming Xu
- Qiong You
- Runmin Guo
- Jianqiang Feng
- Changran Zhang
- Wen Wu
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Affiliations: Department of Cardiology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, P.R. China , Department of Internal Medicine, Huangpu Division of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China, Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P.R. China, Department of Endocrinology, Guangdong Geriatrics Institute, Guangdong General Hospital, Guangzhou, P.R. China
Published online on: August 20, 2012 https://doi.org/10.3892/ijmm.2012.1099
Pages: 1138-1144

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Abstract

Heat shock proteins (HSPs) are critical for adaptation to hypoxia and/or ischemia. Previously, we demonstrated that cobalt chloride (CoCl2), a well-known hypoxia mimetic agent, is an inducer of HSP90. In the present study, we tested the hypothesis that CoCl2-induced upregulation of HSP90 is able to provide cardioprotection in serum and glucose-deprived H9c2 cardiomyocytes (H9c2 cells). Cell viability was detected using a CCK-8 assay, while HSP90 expression was detected via western blotting. The findings of this study showed that serum and glucose deprivation (SGD) induced significant cytotoxicity, overproduction of reactive oxygen species (ROS) and a loss of mitochondrial membrane potential (MMP) in H9c2 cells. In addition, SGD downregulated the expression of HSP90 in a time-dependent manner. The selective inhibitor of HSP90 17-allylamino-17-demethoxygeldanamycin (17-AAG) aggravated SGD-induced cytotoxicity. CoCl2 at 100 µM time-dependently enhanced the expression of HSP90. Treatment with CoCl2 from 50 to 200 µM significantly attenuated cytotoxicity and the downregulation of HSP90 expression induced by SGD for 24 h, respectively. Notably, pretreatment of H9c2 cells with 17-AAG at 2 µM for 60 min before exposure to both CoCl2 (100 µM) and SGD significantly blocked the CoCl2-induced cardioprotective effect, demonstrated by decreased cell viability and MMP loss, as well as increased ROS generation. Taken together, these results suggest that HSP90 may be one of the endogenous defensive mechanisms for resisting ischemia-like injury in H9c2 cells, and that HSP90 plays an important role in chemical hypoxia-induced cardioprotection against SGD-induced injury by its antioxidation and preservation of mitochondrial function.

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