Protection against MPP+ neurotoxicity in cerebellar granule cells by antioxidants
Protection against MPP+ neurotoxicity in cerebellar granule cells by antioxidants
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DOI：
10.1016/j.cellbi.2004.03.005
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发表时间：
2004-01-01
影响因子：
3.9
通讯作者：
Fuentes, JM
中科院分区：
文献类型：
--
作者：
González-Polo, RA;Soler, G;Fuentes, JM
与帕金森病（PD）相关的神经病理学被认为涉及自由基的过度产生、多巴胺自氧化、谷胱甘肽过氧化物酶表达的缺陷、还原型谷胱甘肽水平的减弱、钙稳态的改变、兴奋性毒性和线粒体复合物I活性的遗传缺陷。虽然兴奋性毒素和1-甲基-4-苯基吡啶离子（MPP+）的神经毒性机制有很大不同，但两者都被认为涉及自由基产生、线粒体活性受损和脂质过氧化。我们在这里表明，活性氧（ROS）和活性氮（RNS）的水平显着增加后，培养的小脑颗粒细胞（CGC）与50 μ M MPP+处理。与抗氧化剂如抗坏血酸盐（ASC）、过氧化氢酶、α-生育酚（α-TOH）、辅酶Q（10）（CoQ（10））或超氧化物歧化酶（SOD）共处理使细胞免于MPP+诱导的死亡。MPP+诱导的细胞死亡也被一氧化氮合酶（NOS）抑制剂，如7-硝基吲唑（7-NI），2-乙基-2-硫代嘌呤脲氢溴酸盐（EPTU）或S-甲基异硫脲硫酸盐（MPTU）的共同处理消除。我们还测试了铁螯合剂（甲磺酸去铁胺，DFx）和过氧亚硝酸盐清除剂（FcTTPS）的保护作用，结果进一步支持自由基细胞毒性在MPP+诱导的CGC原代培养物死亡中起重要作用的观点。(C)2004年国际细胞生物学联合会。由爱思唯尔有限公司出版。保留所有权利。
The neuropathology associated with Parkinson's disease (PD) is thought to involve excessive production of free radicals, dopamine autoxidation, defects in glutathione peroxidase expression, attenuated levels of reduced glutathione, altered calcium homeostasis, excitotoxicity and genetic defects in mitochondrial complex I activity. While the neurotoxic mechanisms are vastly different for excitotoxins and 1-methyl-4-phenylpyridinium ion (MPP+), both are thought to involve free radical production, compromised mitochondrial activity and excessive lipid peroxidation. We show here that the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) increased significantly after treatment of cultured cerebellar granule cells (CGCs) with 50 muM MPP+. Co-treatment with antioxidants such as ascorbate (ASC), catalase, alpha-tocopherol (alpha-TOH), coenzyme Q(10) (CoQ(10)) or superoxide dismutase (SOD) rescued the cells from MPP+-induced death. MPP+-induced cell death was also abolished by co-treatment with nitric oxide synthase (NOS) inhibitors such as 7-nitroindazole (7-NI), 2-ethyl-2-thiopseudourea hydrobromide (EPTU) or S-methylisothiourea sulphate (MPTU). We also tested the protective effects of an iron chelator (deferoxamine mesylate, DFx) and a peroxynitrite scavenger (FcTTPS) and the results lend further support to the view that the free radical cytotoxicity plays an essential role in MPP+-induced death in primary cultures of CGC. (C) 2004 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.