Hyperthermic preconditioning protects astrocytes from ischemia/reperfusion injury by up-regulation of HIF-1 alpha expression and binding activity.
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.
Du
Fang
F
Institute for Nautical Medicine and Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, PR China.
Zhu
Li
L
Qian
Zhong-Ming
ZM
Wu
Xiao-Mei
XM
Yung
Wing-Ho
WH
Ke
Ya
Y
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004921:Erythropoietin / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006358:Hot Temperature; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D019194:Ischemic Preconditioning; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D015427:Reperfusion Injury / Q000517:prevention & control; D013997:Time Factors; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; D005904:Glial Fibrillary Acidic Protein; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D004921:Erythropoietin; D007770:L-Lactate Dehydrogenase