Takahashi S, Yamazaki T, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
J Physiol Pharmacol. 1996 Sep;47(3):433-41.
We examined whether or not heat shock and teprenone (a gastric mucosal protective drug), through the induction of heat shock proteins (HSPs), protect cultured rabbit gastric mucosal cells from ethanol-induced damage. Cell viability was assessed by mitochondrial function and membrane permeability assays. Exposure of mucosal cells to 5% ethanol for 1h caused an about 50% reduction in viability. When the cells had been heated at 43 degrees C for 1 h, the cell damage caused by ethanol was significantly prevented. However, pretreatment with teprenone at 1-100 microM failed to prevent the ethanol-induced damage. Western blot analysis with an anti-HSP-72 antibody showed that HSP-72 was apparently induced by heat treatment, but not by teprenone. Both the cytoprotection and induction of HSP-72 on heat treatment were potently inhibited by cycloheximide and actinomycin D. These results demonstrate that, in rabbit gastric mucosal cells, the induction of HSPs is strongly associated with cytoprotection against ethanol-induced damage, but that teprenone has no effect on the cytoprotection or HSP induction.
我们研究了热休克和替普瑞酮(一种胃黏膜保护药物)是否通过诱导热休克蛋白(HSPs)来保护培养的兔胃黏膜细胞免受乙醇诱导的损伤。通过线粒体功能和膜通透性测定评估细胞活力。将黏膜细胞暴露于5%乙醇中1小时会导致活力降低约50%。当细胞在43℃加热1小时后,乙醇引起的细胞损伤得到显著预防。然而,用1 - 100微摩尔的替普瑞酮预处理未能预防乙醇诱导的损伤。用抗HSP - 72抗体进行的蛋白质印迹分析表明,HSP - 72明显由热处理诱导,而非替普瑞酮。环己酰亚胺和放线菌素D均能有效抑制热处理时的细胞保护作用以及HSP - 72的诱导。这些结果表明,在兔胃黏膜细胞中,HSPs的诱导与针对乙醇诱导损伤的细胞保护作用密切相关,但替普瑞酮对细胞保护作用或HSP诱导没有影响。