The effect of Geranylgeranylacetone on renal ischemic/reperfusion injury

香叶基香叶基丙酮对肾缺血/再灌注损伤的影响

• 批准号: 16591598
• 负责人: TSUCHIDA Masahiro
• 金额: $ 2.24万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591598/
• 关键词: Geranylgeranylacetone; Jurkat T cell; apoptosis; Heat shock protein (HSP); ischemic; reperfusion injury; Jurkat T cell; camptothecine; 熱ショック; heat shock protein(HSP); geranylgeranylacetone

Recently geranylgeranylacetone (GGA), an anti gastro-duodenal ulcer drug, has been demonstrated to induce activation of heat shock proteins (HSPs) and renders protection apoptosis in vivo and vitro. However, the molecular mechanisms of anti-apoptotic effects of GGA remain undefined. Thus, we investigated the effect of GGA on camptothecin-induced apoptosis of Jurkat T cells.Agarose-gel electrophoresis showed a typical DNA ladder when the Jurkat cells were exposed to canptothecin at 50 μM for 4 hours. The DNA ladder formation was inhibited, when the cells were pretreated with GGA at 5 μM for 4 hours. Then, the cells were analyzed by Western blotting. Caspase-3,caspase-9 and PARP were cleaved in the cells exposed to camptothecin only. The cells treated with GGA at 5 μM for 4 hours markedly increased the expression of heat shock protein 70 (HSP70) and decreased the camptothecin-induced cleavage of caspase-3,caspase-9 and PARP. These results demonstrate that GGA induced HSP70 and renders protection camptothecin-induced apoptosis in Jurkat cells.

近年来，抗胃十二指肠溃疡药物香叶基香叶基丙酮（GGA）在体内外实验中被证实可诱导热休克蛋白（HSPs）活化，并具有保护细胞凋亡的作用。然而，GGA抗凋亡作用的分子机制仍不清楚。因此，我们研究了GGA对喜树碱诱导的Jurkat T细胞凋亡的影响，当50 μM的喜树碱作用Jurkat T细胞4小时时，琼脂糖凝胶电泳显示典型的DNA梯状条带。5 μM GGA预处理4 h，可抑制DNA梯状条带的形成。然后，通过Western印迹分析细胞。Caspase-3、Caspase-9和PARP在仅暴露于喜树碱的细胞中被切割。5 μM GGA处理4 h后，热休克蛋白70（HSP 70）表达明显增加，Caspase-3、Caspase-9和PARP的裂解明显减少。这些结果表明，GGA诱导HSP 70，并提供保护喜树碱诱导的Jurkat细胞凋亡。