EXPRESSION AND CYTOPROTECTIVE FUNCTION OF HEAT SHOCK PROTEINS IN THE GASTRIC MUCOSA MEDIATED BY CENTRAL NERVOUS SYSTEM-RELATED NEUROPEPTIDES.

本课题研究了热休克蛋白（HSP）在胃粘膜中的表达和细胞保护功能。我们发现，全身应激，如水浸应激，诱导胃粘膜72-kDa热休克蛋白（HSP72）和60-kDa热休克蛋白（HSP60）。在胃黏膜中诱导这些热休克蛋白可增强对0.6N HC1、阿司匹林和乙醇等细胞毒性物质的细胞保护能力。此外，我们发现给药促甲状腺激素释放激素（TRH）特异性诱导胃黏膜HSP72的表达。另一方面，血清素（5-HT）特异性诱导胃黏膜HSP60表达。通过这些特异性诱导方法，我们可以比较这些热休克蛋白的细胞保护能力。HSP72在胃黏膜的诱导表现出较强的粘膜保护能力，而HSP60对细胞毒性药物不具有粘膜保护能力。我们的结果表明，HSP72可能是内源性的胃粘膜细胞保护剂，通过分子伴侣子的功能介导。我们的结论是，hsp72诱导治疗可能对消化性溃疡或药物性胃粘膜损伤有用。

We have studied the expression and cytoprotective function of heat shock protein (HSP) in the gastric mucosa supported by this grant. We have found that systemic stress, such as water-immersion stress, induces 72-kDa heat shock protein (HSP72) and 60-kDa heat shock protein (HSP60) in the gastric mucosa. Induction of these HSPs in the gastric mucosa enhances cytoprotective ability against cytotoxic agents including 0.6N HC1, aspirin and ethanol. Also, we found that administration of tyhrotropin releasing hormone (TRH) specifically induces gastric mucosal HSP72 expression. On the other hand, serotonin (5-HT) specifically induces gastric mucosal HSP60 expression. Using these specific induction methods, we could compare the cytoprotective ability of these HSPs. Whereas HSP72 induction in the gastric mucosa showed strong mucosal protective ability, HSP60 did not have mucosal protective ability against cytotoxic agents. Our results indicate that HSP72 could be endogenous cytoprotectant in the gastric mucosa mediated by the function of molecular chaperon. We concluded that HSP72-induction therapy might be useful for peptic ulcers or drag-induced gastric mucosal damages.