...
【24h】

PPARgamma stimulation promotes mitochondrial biogenesis and prevents glucose deprivation-induced neuronal cell loss.

机译:PPARγ刺激促进线粒体生物发生,并防止葡萄糖剥夺引起的神经元细胞丢失。

获取原文
获取原文并翻译 | 示例
           

摘要

Peroxisome proliferator-activated receptor (PPAR)gamma stimulation provides protection in several models of neurological disorders, but the mechanisms underlying these effects remain to be fully elucidated. Here we have studied whether two PPARgamma agonists, pioglitazone and rosiglitazone, prevent loss of differentiated SH-SY5Y cells transiently exposed to glucose deprivation (GD). Nanomolar drug concentrations prevented GD-induced cell loss in a concentration- and time-dependent manner. These effects were abolished by malonate, a reversible mitochondrial Complex II inhibitor, while significantly potentiated by pyruvate, thus suggesting that they are related to mitochondrial function. During cell pretreatment, PPARgamma agonists promoted biogenesis of functional mitochondria, as indicated by the up-regulation of PPARgamma coactivator (PGC)-1alpha, NRF1, TFAM, cytochrome c oxidase subunit (CO) I and CO IV, and the increased level of mtDNA, while did not significantly change mitochondrial membrane potential. In addition, the analysis of the concentration-response and time-course curves for the protective effects and the up-regulation of mitochondrial biogenesis markers suggests that mitochondrial biogenesis and cell loss prevention are related effects. In conclusion our data indicate that a prolonged PPARgamma stimulation, by repeated administration of nanomolar pioglitazone or rosiglitazone concentrations, decreases GD-induced loss of differentiated SH-SY5Y cells. In addition, they suggest that mitochondrial biogenesis may contribute to these effects.
机译:过氧化物酶体增殖物激活受体(PPAR)γ刺激可在几种神经系统疾病模型中提供保护,但这些作用的潜在机制尚待充分阐明。在这里,我们研究了两种PPARgamma激动剂吡格列酮和罗格列酮是否可以防止瞬时暴露于葡萄糖剥夺(GD)的分化的SH-SY5Y细胞丢失。纳摩尔浓度的药物以浓度和时间依赖性的方式阻止了GD诱导的细胞丢失。这些作用被丙二酸酯(一种可逆的线粒体复合物II抑制剂)消除,而被丙酮酸显着增强,因此表明它们与线粒体功能有关。在细胞预处理过程中,PPARgamma激动剂可促进功能性线粒体的生物发生,如PPARgamma辅助激活剂(PGC)-1alpha,NRF1,TFAM,细胞色素c氧化酶亚基(CO)I和CO IV的上调以及mtDNA水平的升高所表明的,虽然没有明显改变线粒体膜电位。此外,对浓度-响应曲线和时程曲线的保护作用和线粒体生物发生标志物上调的分析表明,线粒体生物发生与细胞丢失的预防是相关的作用。总之,我们的数据表明,通过重复施用纳摩尔浓度的吡格列酮或罗格列酮浓度,延长的PPARγ刺激可降低GD诱导的分化SH-SY5Y细胞的损失。此外,他们认为线粒体的生物发生可能有助于这些作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号