依普卡林通过开放线粒体ATP敏感性钾通道保护PC12细胞免受H2O2诱导的氧化损伤。

Iptakalim protects PC12 cell against H2O2-induced oxidative injury via opening mitochondrial ATP-sensitive potassium channel.

作者信息

Chai Yi, Niu Ling, Sun Xiu-Lan, Ding Jian-Hua, Hu Gang

机构信息

Laboratory of Neuropharmacology, Department of Anatomy, Histology and Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China.

出版信息

Biochem Biophys Res Commun. 2006 Nov 17;350(2):307-14. doi: 10.1016/j.bbrc.2006.09.045. Epub 2006 Sep 20.

DOI:10.1016/j.bbrc.2006.09.045

PMID:17010314

Abstract

The final common pathway in the demise of dopaminergic neurons in Parkinson's disease may involve oxidative stress and excitotoxicity. In this study, we examined the neuroprotective effects of a novel ATP-sensitive potassium channel (K(ATP)) opener, iptakalim (IPT), against H(2)O(2)-induced cytotoxicity in rat dopaminergic PC12 cells. Pretreatment with IPT could attenuate increased extracellular glutamate levels and inhibit calcium influxing induced by H(2)O(2). Moreover, IPT regulated the expressions of bcl-2 and bax which were responsible for inhibiting apoptosis in PC12 cells. These protective effects of IPT were abolished by selective mitoK(ATP) channel blocker 5-hydroxydecanoate. Therefore, IPT can protect PC12 cells against H(2)O(2)-induced oxidative injury via activating mitoK(ATP) channel.

摘要

帕金森病中多巴胺能神经元死亡的最终共同途径可能涉及氧化应激和兴奋性毒性。在本研究中，我们检测了一种新型ATP敏感性钾通道（K(ATP)）开放剂伊普卡林（IPT）对H(2)O(2)诱导的大鼠多巴胺能PC12细胞毒性的神经保护作用。IPT预处理可减轻细胞外谷氨酸水平的升高，并抑制H(2)O(2)诱导的钙内流。此外，IPT调节了负责抑制PC12细胞凋亡的bcl-2和bax的表达。选择性线粒体K(ATP)通道阻滞剂5-羟基癸酸可消除IPT的这些保护作用。因此，IPT可通过激活线粒体K(ATP)通道保护PC12细胞免受H(2)O(2)诱导的氧化损伤。