L-carnitine protects against nickel-induced neurotoxicity by mitochondrial function in Neuro-2a cells
L-carnitine protects against nickel-induced neurotoxicity by mitochondrial function in Neuro-2a cells
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DOI：
10.1016/j.taap.2011.03.008
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发表时间：
2011-05-15
影响因子：
3.8
通讯作者：
Zhou, Zhou
中科院分区：
文献类型：
--
作者：
He, Min-Di;Xu, Shang-Cheng;Zhou, Zhou
线粒体功能障碍被认为是镍诱导的神经毒性机制的一部分。L-肉碱（LC）是一种由赖氨酸和蛋氨酸生物合成的季铵化合物，通过改善线粒体能量和功能表现出其神经保护作用。本研究的目的是探讨LC是否可以有效地保护镍诱导的神经毒性。在这里，我们暴露于不同浓度的氯化镍（NiCl 2）（0.25，0.5，1和2 mM）的小鼠神经母细胞瘤细胞系（神经-2a）24小时，或0.5 mM和1 mM NiCl 2的各种时期（0，3，6，12，或24小时）。我们发现，镍显着增加细胞活力的损失和乳酸脱氢酶（LDH）的释放在神经2a细胞。此外，镍暴露显著升高了活性氧（ROS）和丙二醛（MDA）水平，破坏了线粒体膜电位（Delta Psi（m）），降低了腺苷-5 '-三磷酸（ATP）浓度，降低了线粒体DNA（mtDNA）拷贝数和mtDNA转录水平。然而，所有的细胞毒性和线粒体功能障碍，由镍引发的有效衰减预处理与LC。LC的这些保护作用可能归因于其在镍处理的细胞中维持线粒体功能的作用。我们的研究结果表明，LC可能有很大的药理潜力，在保护对镍在神经系统中的不利影响。(C)2011 Elsevier Inc. All rights reserved.
Mitochondrial dysfunction is thought to be a part of the mechanism underlying nickel-induced neurotoxicity. L-carnitine (LC), a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine in all mammalian species, manifests its neuroprotective effects by improving mitochondrial energetics and function. The purpose of this study was to investigate whether LC could efficiently protect against nickel-induced neurotoxicity. Here, we exposed a mouse neuroblastoma cell line (Neuro-2a) to different concentrations of nickel chloride (NiCl2) (0.25, 0.5, 1, and 2 mM) for 24 h, or to 0.5 mM and 1 mM NiCl2 for various periods (0, 3, 6, 12, or 24 h). We found that nickel significantly increased the cell viability loss and lactate dehydrogenase (LDH) release in Neuro-2a cells. In addition, nickel exposure significantly elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, disrupted the mitochondrial membrane potential (Delta Psi(m)), reduced adenosine-5'-triphosphate (ATP) concentrations and decreased mitochondrial DNA (mtDNA) copy numbers and mtRNA transcript levels. However, all of the cytotoxicities and mitochondrial dysfunctions that were triggered by nickel were efficiently attenuated by pretreatment with LC. These protective effects of LC may be attributable to its role in maintaining mitochondrial function in nickel-treated cells. Our results suggest that LC may have great pharmacological potential in protecting against the adverse effects of nickel in the nervous system. (C) 2011 Elsevier Inc. All rights reserved.