NO에 의한 HSP10 AND HSP60 유전자의 발현 억제 기전

초록

The administration of the aminoguanidine (AG), an inhibitor of the inducible nitric oxide synthesis (iNOS), reduces ischemic damage in the animal model of transient middle cerebral artery occlusion (MCAO). We examined the expressional regulation of the small heat shock proteins, such as HSP10 and HSP60, in postischemic brain. In postischemic brain, NO induction is suppressed by AG administration and significant reduction of the infarct volume was accompanied by it. The levels of expression of HSP10 and HSP60 were significantly induced in postischemic brain, which were further up-regulated in AG-administered animals. The result suggests that HSP10 and HSP60 are induced in postischemic brain, but they are under the down-regulation by NO, which has been known to be secreted beginning 12 hours after the MCAO/reperfusion. Induction and regulation of small heat shock proteins were detected in neurons and astrocytes located in peri-infarct region of the brain. Down-regulation of the HSP10 and HSP60 by NO was confirmed in in vitro experiments, wherein LPS-induced HSP10 and SHP60 expression in C6 glioma cells was further up-regulated by NMMA treatment. To evaluate the promoter region responsible for the down-regulation, reporter gene studied using about 500 bp promoter region of HSP10 and HSP60 genes are underway in C6 glioma cell line.