Hyperthermic preconditioning protects astrocytes from ischemia/reperfusion injury by up-regulation of HIF-1 alpha expression and binding activity |
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Authors: | Fang Du Li Zhu Zhong-Ming Qian Xiao-Mei Wu Wing-Ho Yung Ya Ke |
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Affiliation: | 1. Institute for Nautical Medicine and Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, PR China;2. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong;3. Department of Applied Biology & Chemical Technology and National Key Laboratory of CMMP (Shenzhen), Hong Kong Polytechnic University, Kowloon, Hong Kong |
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Abstract: | It has been demonstrated that hypoxia-inducible factor-1 alpha (HIF-1 alpha) mediates ischemic tolerance induced by hypoxia/ischemia or pharmacological preconditioning. In addition, preconditioning stimuli can be cross-tolerant, safeguarding against other types of injury. We therefore hypothesized HIF-1 alpha might also be associated with ischemic tolerance induced by hyperthermic preconditioning. In the present study, we demonstrated for the first time that 6 h of hyperthermia (38 °C or 40 °C) could induce a characteristic “reactive” morphology and a significant increase in the expression of bystin in astrocytes. We also showed that pre-treatment with 6 h of hyperthermia resulted in a significant increase in cell viability and a remarkable decrease in lactate dehydrogenase (LDH) release and apoptosis development in the astrocytes that were exposed to 24 h of ischemia and a subsequent 24 h of reperfusion. Analysis of mechanisms showed that hyperthermia could lead to a significant increase in HIF-1 alpha expression and also the HIF-1 binding activity in the ischemia/reperfusion astrocytes. The data provide evidence to our hypothesis that the up-regulation of HIF-1 alpha is associated with the protective effects of hyperthermic preconditioning on astrocytes against ischemia/reperfusion injury. |
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