Preinduction of HSP70 promotes hypoxic tolerance and facilitates acclimatization to acute hypobaric hypoxia in mouse brain |
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Authors: | Kuan Zhang Tong Zhao Xin Huang Zhao-hui Liu Lei Xiong Ming-ming Li Li-ying Wu Yong-qi Zhao Ling-ling Zhu Ming Fan |
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Institution: | (1) Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing, 100850, China |
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Abstract: | It has been shown that induction of HSP70 by administration of geranylgeranylacetone (GGA) leads to protection against ischemia/reperfusion
injury. The present study was performed to determine the effect of GGA on the survival of mice and on brain damage under acute
hypobaric hypoxia. The data showed that the mice injected with GGA survived significantly longer than control animals (survival
time of 9.55 ± 3.12 min, n = 16 vs. controls at 4.28 ± 4.29 min, n = 15, P < 0.005). Accordingly, the cellular necrosis or degeneration of the hippocampus and the cortex induced by sublethal hypoxia
for 6 h could be attenuated by preinjection with GGA, especially in the CA2 and CA3 regions of the hippocampus. In addition,
the activity of nitric oxide synthase (NOS) of the hippocampus and the cortex was increased after exposure to sublethal hypoxia
for 6 h but could be inhibited by the preinjection of GGA. Furthermore, the expression of HSP70 was significantly increased
at 1 h after GGA injection. These results suggest that administration of GGA improved survival rate and prevented acute hypoxic
damage to the brain and that the underlying mechanism involved induction of HSP70 and inhibition of NOS activity. |
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Keywords: | Acute hypobaric hypoxia Brain damage Geranylgeranylacetone Heat shock protein 70 Nitrogen monoxidum synthase Survival |
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