Down-regulation of the expression of the HSP10 and Hsp60 by NO

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). To examine the expressional regulation of the small heat shock proteins, such as HSP10 and HSP60, in postischemic brain, we first established the animal model, in which NO induction is suppressed by AG administeratiom and significant reduction of the infract 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. Reporter gene studied using about 500 bp promoter region of HSP10 and HSP60 genes in C6 glioma cell line revealed that NO down-regulates sHSP expression at transcription level probably via heat shock element (HSE) region localized in the promoter of those genes. Investigation of the signaling mechanism regulating the transcriptional down regulation by NO is underway.