In vitro inhibition of lysine decarboxylase activity by organophosphate esters

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

	In vitro inhibition of lysine decarboxylase activity by organophosphate esters
	Wang, Sufang ; Wan, Bin ; Zhang, Lianying ; Yang, Yu ; Guo, Liang-Hong
刊名	BIOCHEMICAL PHARMACOLOGY
	2014
卷号	92 期号:3 页码:506-516
关键词	Organophosphate esters Toxicity Lysine decarboxylase Inhibition Molecular docking
ISSN号	0006-2952
中文摘要	Organophosphate esters (OPEs), a major group of organophosphorus flame retardants, are regarded as emerging environmental contaminants of health concern. Amino acid decarboxylases catalyze the conversion of amino acids into polyamines that are essential for cell proliferation, hypertrophy and tissue growth. In this paper, inhibitory effect of twelve OPEs with aromatic, alkyl or chlorinated alkyl substituents on the activity of lysine decarboxylase (LDC) was assessed quantitatively with an economic and label-free fluorescence sensor and cell assay. The sensor comprises a macrocyclic host (cucurbit[7]uril) and a fluorescent dye (acridine orange) reporter. The twelve OPEs were found to vary in their capacity to inhibit LDC activity. Alkyl group substituted OPEs had no inhibitory effect. By contrast, six OPEs substituted with aromatic or chlorinated alkyl groups inhibited LDC activity significantly with IC50 ranging from 1.32 mu M to 9.07 mu M. Among them, the inhibitory effect of tri-m-cresyl phosphate (TCrP) was even more effective as an inhibitor than guanosine 5'-diphosphate-3'-diphosphate (ppGpp) (1.60 mu M), an LDC natural inhibitor in vivo. Moreover, at non-cytotoxic concentrations, these six OPEs showed perceptible inhibitory effects on LDC activity in PC12 living cells, and led to a marked loss in the cadaverine content. Molecular docking analysis of the LDC/OPE complexes revealed that different binding modes contribute to the difference in their inhibitory effect. Our finding suggested that LDC, as a new potential biological target of OPEs, might be implicated in toxicological and pathogenic mechanism of OPEs. (C) 2014 Elsevier Inc. All rights reserved.
WOS记录号	WOS:000345955400012
公开日期	2015-03-24
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/9388]
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,Wan, Bin,Zhang, Lianying,et al. In vitro inhibition of lysine decarboxylase activity by organophosphate esters[J]. BIOCHEMICAL PHARMACOLOGY,2014,92(3):506-516.
APA	Wang, Sufang,Wan, Bin,Zhang, Lianying,Yang, Yu,&Guo, Liang-Hong.(2014).In vitro inhibition of lysine decarboxylase activity by organophosphate esters.BIOCHEMICAL PHARMACOLOGY,92(3),506-516.
MLA	Wang, Sufang,et al."In vitro inhibition of lysine decarboxylase activity by organophosphate esters".BIOCHEMICAL PHARMACOLOGY 92.3(2014):506-516.