Preinduction of HSP70 promotes hypoxic tolerance and facilitates acclimatization to acute hypobaric hypoxia in mouse brain.
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.
Zhang
Kuan
K
Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing, China.
Zhao
Tong
T
Huang
Xin
X
Liu
Zhao-hui
ZH
Xiong
Lei
L
Li
Ming-ming
MM
Wu
Li-ying
LY
Zhao
Yong-qi
YQ
Zhu
Ling-ling
LL
Fan
Ming
M
D000064:Acclimatization; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D004224:Diterpenes / Q000008:administration & dosage; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism* / Q000502:physiology; D006624:Hippocampus / Q000473:pathology; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015996:Survival Rate
D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D019001:Nitric Oxide Synthase; C031049:geranylgeranylacetone