Differential effect of catecholamines and MPP+ on membrane permeability in brain mitochondria and cell viability in PC 12 cells
Differential effect of catecholamines and MPP+ on membrane permeability in brain mitochondria and cell viability in PC 12 cells
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DOI：
10.1016/s0197-0186(01)00069-9
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发表时间：
2002-04-01
影响因子：
4.2
通讯作者：
Han, ES
中科院分区：
文献类型：
--
作者：
Lee, CS;Han, JH;Han, ES
本研究探讨了多巴胺，6-羟基多巴胺（6-OHDA），和MPP+对脑线粒体膜通透性转换和PC 12细胞活力的影响。多巴胺和6-羟基多巴胺引起线粒体肿胀和膜电位变化，这是由另外的抗氧化酶，SOD和过氧化氢酶抑制。相反，抗氧化酶并没有减少MPP+对线粒体肿胀和膜电位的影响。儿茶酚胺能促进线粒体Ca ~（2+）的摄取和释放，MPP ~+能诱导线粒体Ca ~（2+）的释放。儿茶酚胺诱导线粒体中的巯基氧化，其被抗氧化酶降低。MPP+对线粒体细胞色素c的释放影响不大，不引起巯基氧化。儿茶酚胺和MPP+诱导的细胞死亡，包括细胞凋亡，在PC 12细胞中，通过添加抗氧化酶抑制。结果提示，多巴胺和6-羟基多巴胺的氧化可调节脑线粒体膜通透性，诱导PC 12细胞死亡，这可能与氧化应激有关。MPP+对神经细胞的毒性作用与儿茶酚胺不同。(C)2002爱思唯尔科技有限公司版权所有。
The present study examined the effect of dopamine, 6-hydroxydopamine (6-OHDA), and MPP+ on the membrane permeability transition in brain mitochondria and on viability in PC12 cells. Dopamine and 6-hydroxydopamine induced the swelling and membrane potential change in mitochondria, which was inhibited by addition of antioxidant enzymes, SOD and catalase. In contrast, antioxidant enzymes did not reduce the effect of MPP+ on mitochondrial swelling and membrane potential. Catecholamines enhanced the Ca2+ uptake and release by mitochondria, and the addition of MPP+ induced Ca2+ release. Catecholamines induced a thiol oxidation in mitochondria that was decreased by antioxidant enzymes. MPP+ showed a little effect on the cytochrome c release from mitochondria and did not induce thiol oxidation. Catecholamines and MPP+ induced a cell death, including apoptosis, in PC12 cells that was inhibited by addition of antioxidant enzymes. The result suggests that the oxidation of dopamine and 6-hydroxydopamine could modulate the membrane permeability in brain mitochondria and induce PC12 cell death, which may be ascribed to oxidative stress. MPP+ appears to exert a toxic effect on neuronal cells by the action, which is different from catecholamines. (C) 2002 Elsevier Science Ltd. All rights reserved.