Arginine decarboxylase: A novel biological target of mercury compounds identified in PC12 cells

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Arginine decarboxylase: A novel biological target of mercury compounds identified in PC12 cells
	Wang, Sufang; Lv, Qiyan; Yang, Yu; Guo, Liang-Hong; Wan, Bin; Ren, Xiaomin; Zhang, Hui
刊名	BIOCHEMICAL PHARMACOLOGY
	2016-10-15
卷号	118 期号:0 页码:109-120
关键词	Mercury Neurotoxicity Arginine decarboxylase Inhibition Molecular dynamics simulation
英文摘要	Mercury compounds are well-known toxic environmental pollutants and potently induce severe neurotoxicological effects in human and experimental animals. Previous studies showed that one of the mechanisms of mercury compounds neurotoxicity arose from the over-activation of the N-methyl D-aspartate (NMDA)-type glutamate receptor induced by increased glutamate release. In this work, we aimed to investigate the molecular mechanisms of Hg compounds neurotoxicities by identifying their biological targets in cells. Firstly, the inhibitory effects of four Hg compounds, including three organic (methyl-, ethyl- and phenyl-mercury) and one inorganic (Hg2+) Hg compounds, on the activity of arginine decarboxylase (ADC), a key enzyme in the central agmatinergic system, were evaluated. They were found to inhibit the ADC activity significantly with methylmercury (MeHg) being the strongest (IC50 = 7.96 nM). Furthermore, they showed remarkable inhibitory effects on ADC activity in PC12 cells (MeHg > EtHg > PhHg > HgCl2), and led to a marked loss in the level of agmatine, an endogenous neuro-modulatory and neuroprotective agent that selectively blocks the activation of NMDA receptors. MeHg was detected in the immunoprecipitated ADC from the cells, providing unequivocal evidence for the direct binding of MeHg with ADC in the cell. Molecular dynamics simulation revealed that Hg compounds could form the coordination bond not only with cofactor PLP of ADC, but also with substrate arginine. Our finding indicated that MeHg could attenuate the neuroprotective effects of agmatine by the inhibition of ADC, a new cellular target of MeHg, which might be implicated in molecular mechanism of MeHg neurotoxicity. (C) 2016 Elsevier Inc. All rights reserved.
收录类别	SCI
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/35803]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Wang, Sufang,Lv, Qiyan,Yang, Yu,et al. Arginine decarboxylase: A novel biological target of mercury compounds identified in PC12 cells[J]. BIOCHEMICAL PHARMACOLOGY,2016,118(0):109-120.
APA	Wang, Sufang.,Lv, Qiyan.,Yang, Yu.,Guo, Liang-Hong.,Wan, Bin.,...&Zhang, Hui.(2016).Arginine decarboxylase: A novel biological target of mercury compounds identified in PC12 cells.BIOCHEMICAL PHARMACOLOGY,118(0),109-120.
MLA	Wang, Sufang,et al."Arginine decarboxylase: A novel biological target of mercury compounds identified in PC12 cells".BIOCHEMICAL PHARMACOLOGY 118.0(2016):109-120.