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

Du Fang (1, 2) , Zhu Li (1, 3) , Qian Zhong Ming (1, 3) , Wu Xiao Mei (1, 2) , Ke Ya (1, 2)

1 Nantong University
2 Faculty of Medicine
3 Department of Applied Biology & Chemical Technology and National Key Laboratory of CMMP (Shenzhen)

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 hours 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 hours 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 hours of ischemia and a subsequent 24 hours 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.

Mots clés: Hyperthermiac preconditioning; ischemia/reperfusion; reactive astrocytes; hypoxia-inducible factor-1 alpha (HIF-1 alpha); apoptosis; cell viability; lactate dehydrogenase (LDH)

Du Fang, Zhu Li, Qian Zhong Ming, Wu Xiao Mei, Ke Ya. 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, 2010, 1802 (11), pp.1048. ⟨10.1016/j.bbadis.2010.06.013⟩. ⟨hal-00623311⟩