首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Preventive effects of imperatorin on perfluorohexanesulfonate-induced neuronal apoptosis via inhibition of intracellular calcium-mediated ERK pathway
【24h】

Preventive effects of imperatorin on perfluorohexanesulfonate-induced neuronal apoptosis via inhibition of intracellular calcium-mediated ERK pathway

机译:Imperatorin通过抑制细胞内钙介导的ERK途径对全氟己烷磺酸盐诱导的神经元凋亡的预防作用

获取原文
           

摘要

Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from seven-day old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxS-induced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway.
机译:早年神经元暴露于环境毒物已被认为是神经退行性疾病发展的重要病因。全氟己烷磺酸盐(PFHxS)是主要的全氟烷基化合物之一,是分布广泛的环境污染物。我们已经报道了PFHxS通过ERK介导的途径诱导神经元凋亡。 Imperatorin是在各种食用植物中发现的呋喃香豆素,具有广泛的药理作用,包括神经保护作用。在这项研究中,使用小脑颗粒细胞(CGC)检查了欧前胡素对PFHxS诱导的神经元凋亡及其潜在机制的影响。从七日龄大鼠中分离出CGC,使其在培养中生长七天。 Caspase-3活性和TUNEL染色用于确定神经元凋亡。欧前胡素和ERK通路抑制剂PD98059显着降低了PFHxS诱导的CGC细胞凋亡。 PFHxS诱导细胞内钙的持续增加,这被欧前胡素,NMDA受体拮抗剂,MK801和L型电压依赖性钙通道阻滞剂,地尔硫卓和硝苯地平显着阻断。 PFHxS对caspase-3的激活也被MK801,地尔硫卓和硝苯地平抑制。欧前胡素,MK801,地尔硫卓和硝苯地平抑制PFHxS增加的ERK活化。总之,欧前胡素通过抑制NMDA受体/细胞内钙介导的ERK途径,保护CGC免受PFHxS诱导的细胞凋亡。

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