Inhibitory effects of cigarette smoke on glial inducible nitric oxide synthase and lack of protective properties against oxidative neurotoxins in vitro
Inhibitory effects of cigarette smoke on glial inducible nitric oxide synthase and lack of protective properties against oxidative neurotoxins in vitro
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DOI：
10.1016/j.neuro.2004.07.005
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发表时间：
2005-01-01
期刊：
影响因子：
3.4
通讯作者：
Soliman, KFA
中科院分区：
文献类型：
--
作者：
Mazzio, EA;Kolta, MG;Soliman, KFA
流行病学研究一直报告吸烟与帕金森氏病(PD)的相关风险之间存在负相关。多巴胺能神经元的变性可能与胶质细胞单胺氧化酶(MAO)和诱导型一氧化氮合酶(INOS)的有毒代谢产物有关。本研究评价香烟烟雾对MAO潜在神经毒性产物1-甲基-4-苯基吡啶(MPP+)、6-羟基多巴胺(6-OHDA)和过氧化氢(H_2O_2)在脑神经母细胞瘤中的直接保护作用。此外，还观察了CS对内毒素/细胞因子激活的胶质瘤iNOS蛋白表达和MAO酶活性的影响。香烟烟雾冷凝物(CSCs)来自万宝路20 A类香烟和肯塔基州2R4F参考研究(2R4F)香烟。CSCs对神经母细胞瘤中的6-OHDA或H_2O_2毒性没有保护作用，对MPP+表现出非常温和的保护作用[类似于10%]。两种CSC都没有表现出抗氧化能力，但相反，CSC中含有高浓度的NO2_2。矛盾的是，在胶质瘤细胞中，iNOS蛋白的表达和内源性酶NO2_2的产生都被两种CSCs显著抑制。两种CSCs对脑胶质瘤MAO-A和MAO-B也有抑制作用[1.4.3.4]。动力学分析表明，2R4F-CSC表现为竞争性抑制，而万宝路-CSC表现为竞争性和非竞争性抑制。总而言之，这些数据表明，香烟烟雾似乎并不能直接预防所选神经毒素的毒性。相反，CS对神经胶质细胞有明显的作用，因此它的存在可以同时减弱细胞因子对iNOS和MAO的诱导。(C)2004 Elsevier Inc.保留所有权利。
Epidemiological studies consistently report an inverse correlation between cigarette smoking and associated risk for Parkinson's disease (PD). The degeneration of dopaminergic neurons may involve the toxic metabolic products of glial cell monoamine oxidase (MAO) and inducible nitric oxide synthase (iNOS). This study evaluates the direct protective effects of cigarette smoke (CS) against potential neurotoxic products of MAO, such as 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA) and hydrogen peroxide (H2O2) in brain neuroblastoma. Moreover, the effects of CS were also evaluated on endotoxin/cytokine activated glioma iNOS protein expression and MAO enzyme activity. Cigarette smoke condensates (CSCs) were acquired from Marlboro 20 Class A and Kentucky 2R4F reference research (2R4F) cigarettes. The CSCs did not protect against 6-OHDA or H2O2 toxicity in neuroblastoma, and exhibited a very mild protective effect [similar to10%] against MPP+. Neither CSC demonstrated antioxidant capability, but conversely contained high concentration of NO2_. Paradoxically, in glioma cells, iNOS protein expression and endogenous enzymatic NO2_ production were significantly blocked by both CSCs. Both CSCs also inhibited glioma MAO-A and MAO-B [1.4.3.4]. Kinetic analysis indicated that 2R4F-CSC displayed competitive inhibition and the Marlboro-CSC exertedpotent competitive and non-competitive inhibition. In conclusion, these data suggest that cigarette smoke does not appear to directly protect against the toxicity of the selected neurotoxins. In contrast, CS exerts pronounced effects on glia, whereby its presence can simultaneously attenuate cytokine induction of iNOS and MAO. (C) 2004 Elsevier Inc. All rights reserved.