Hyperthermic preconditioning protects astrocytes from ischemia/reperfusion injury by up-regulation of HIF-1 alpha expression and binding activity

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1802

Article

Du, Fang^1,2,3  Zhu, Li^2,3,4,5  Qian, Zhong-Ming^2,3,4,5  Wu, Xiao-Mei^1,2,3  Yung, Wing-Ho¹  Ke, Ya¹ 

[1] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Shatin, Hong Kong, Peoples R China

[2] Nantong Univ, Inst Naut Med, Nantong 226001, Peoples R China

[3] Nantong Univ, Jiangsu Key Lab Neuroregenerat, Nantong 226001, Peoples R China

[4] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Kowloon, Hong Kong, Peoples R China

[5] Hong Kong Polytech Univ, Natl Key Lab CMMP Shenzhen, Kowloon, Hong Kong, Peoples R China

关键词: Hyperthermiac preconditioning;    Ischemia/reperfusion;    Reactive astrocytes;    Hypoxia-inducible factor-1 alpha (HIF-1 alpha);    Apoptosis;    Cell viability;    Lactate dehydrogenase (LDH);   

DOI  :  10.1016/j.bbadis.2010.06.013

来源: Elsevier

【 摘 要 】

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 degrees C or 40 degrees 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 (C) 2010 Elsevier B.V. All rights reserved

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