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Crocin suppresses tumor necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells.

机译:番红花抑制肿瘤坏死因子-α诱导的神经元分化的PC-12细胞的细胞死亡。

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摘要

Crocus sativus L. is used in Chinese traditional medicine to treat some disorders of the central nervous system. Crocin is an ethanol-extractable component of Crocus sativus L.; it is reported to prevent ethanol-induced impairment of learning and memory in mice. In this study, we demonstrate that crocin suppresses the effect of tumor necrosis factor (TNF)-alpha on neuronally differentiated PC-12 cells. PC-12 cells dead from exposure to TNF-alpha show apoptotic morphological changes and DNA fragmentation. These hallmark features of cell death did not appear in cells treated in the co-presence of 10 microM crocin. Moreover, crocin suppressed the TNF-alpha-induced expression of Bcl-Xs and LICE mRNAs and simultaneously restored the cytokine-induced reduction of Bcl-X(L) mRNA expression. The modulating effects of crocin on the expression of Bcl-2 family proteins led to a marked reduction of a TNF-alpha-induced release of cytochrome c from the mitochondria. Crocin also blocked the cytochrome c-induced activation of caspase-3. To learn how crocin exhibits these anti-apoptotic actions in PC-12 cells, we tested the effect of crocin on PC-12 cell death induced by daunorubicin. We found that crocin inhibited the effect of daunorubicin as well. Our findings suggest that crocin inhibits neuronal cell death induced by both internal and external apoptotic stimuli.
机译:藏红花(Crocus sativus L.)在中药中用于治疗中枢神经系统的某些疾病。番红花是番红花的乙醇提取成分。据报道可以预防乙醇引起的小鼠学习和记忆障碍。在这项研究中,我们证明了番红花抑制肿瘤坏死因子(TNF)-α对神经元分化的PC-12细胞的作用。因暴露于TNF-α而死亡的PC-12细胞显示出凋亡的形态变化和DNA片段化。这些细胞死亡的标志性特征未在同时存在10 microM crocin的细胞中出现。此外,番红花抑制了TNF-α诱导的Bcl-Xs和LICE mRNA的表达,同时恢复了细胞因子诱导的Bcl-X(L)mRNA表达的降低。番红花对Bcl-2家族蛋白表达的调节作用导致TNF-α诱导的线粒体细胞色素c释放的明显减少。番红花还阻断了细胞色素c诱导的caspase-3活化。为了了解藏红花素如何在PC-12细胞中表现出这些抗凋亡作用,我们测试了藏花红素对柔红霉素诱导的PC-12细胞死亡的影响。我们发现藏红花素也抑制柔红霉素的作用。我们的发现表明,番红花抑制由内部和外部凋亡刺激诱导的神经元细胞死亡。

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