Chloroacetic acid induced neuronal cells death through oxidative stress-mediated p38-MAPK activation pathway regulated mitochondria-dependent apoptotic signals

doi:10.1016/j.tox.2012.10.008

中山醫學大學機構典藏 CSMUIR > 健康管理學院 > 職業安全衛生學系暨碩士班 > 期刊論文 > Item 310902500/20317

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/20317

Title:	Chloroacetic acid induced neuronal cells death through oxidative stress-mediated p38-MAPK activation pathway regulated mitochondria-dependent apoptotic signals
Authors:	Chen, Chun-Hung Chen, Sz-Jie Su, Chin-Chuan Yen, Cheng-Chieh Tseng, To-Jung Jinn, Tzyy-Rong Tang, Feng-Cheng Chen, Kuo-Liang Su, Yi-Chang Lee, kuan-I Hung, Dong-Zong Huang, Chun-Fa
Keywords:	Chloroacetic acid (CA);Neurotoxicity;Apoptosis;Oxidative stress;Mitochondrial dysfunction;p38-MAPK
Date:	2013
Issue Date:	2019-08-15T08:29:15Z (UTC)
Publisher:	Toxicology
ISSN:	0300-483X
Abstract:	Chloroacetic acid (CA), a toxic chlorinated analog of acetic acid, is widely used in chemical industries as an herbicide, detergent, and disinfectant, and chemical intermediates that are formed during the synthesis of various products. In addition, CA has been found as a by-product of chlorination disinfection of drinking water. However, there is little known about neurotoxic injuries of CA on the mammalian, the toxic effects and molecular mechanisms of CA-induced neuronal cell injury are mostly unknown. In this study, we examined the cytotoxicity of CA on cultured Neuro-2a cells and investigated the possible mechanisms of CA-induced neurotoxicity. Treatment of Neuro-2a cells with CA significantly reduced the number of viable cells (in a dose-dependent manner with a range from 0.1 to 3 mM), increased the generation of ROS, and reduced the intracellular levels of glutathione depletion. CA also increased the number of sub-G1 hypodiploid cells; increased mitochondrial dysfunction (loss of MMP, cytochrome c release, and accompanied by Bcl-2 and Mcl-1 down-regulation and Bax up-regulation), and activated the caspase cascades activations, which displayed features of mitochondria-dependent apoptosis pathway. These CA-induced apoptosis-related signals were markedly prevented by the antioxidant N-acetylcysteine (NAC). Moreover, CA activated the JNK and p38-MAPK pathways, but did not that ERK1/2 pathway, in treated Neuro-2a cells. Pretreatment with NAC and specific p38-MAPK inhibitor (SB203580), but not JNK inhibitor (SP600125) effectively abrogated the phosphorylation of p38-MAPK and attenuated the apoptotic signals (including: decrease in cytotoxicity, caspase-3/-7 activation, the cytosolic cytochrome c release, and the reversed alteration of Bcl-2 and Bax mRNA) in CA-treated Neuro-2a cells. Taken together, these data suggest that oxidative stress-induced p38-MAPK activated pathway-regulated mitochondria-dependent apoptosis plays an important role in CA-caused neuronal cell death.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/20317
Relation:	Toxicology, vol. 303, 72 -82
Appears in Collections:	[職業安全衛生學系暨碩士班] 期刊論文

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