Cellular target recognition of perfluoroalkyl acids: In vitro evaluation of inhibitory effects on lysine decarboxylase
Cellular target recognition of perfluoroalkyl acids: In vitro evaluation of inhibitory effects on lysine decarboxylase
复制标题
全氟烷基酸的细胞靶标识别：赖氨酸脱羧酶抑制作用的体外评价
DOI：
10.1016/j.scitotenv.2014.07.034
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发表时间：
2014
影响因子：
9.8
通讯作者：
Zhao Lixia
中科院分区：
文献类型：
--
作者：
Wang Sufang;Lv Qiyan;Yang Yu;Guo Liang-Hong;Wan Bin;Zhao Lixia
Perfluoroalkyl acids (PFAAs) have been shown to bind with hepatic peroxisome proliferator receptor α, estrogen receptors and human serum albumin and subsequently cause some toxic effects. Lysine decarboxylase (LDC) plays an important role in cell growth and developmental processes. In this study, the inhibitory effect of 16 PFAAs, including 13 perfluorinated carboxylic acids (PFCAs) and 3 perfluorinated sulfonic acids (PFSAs), on lysine decarboxylase (LDC) activity was investigated. The inhibition constants obtained in fluorescence enzyme assays fall in the range of 2.960 μM to 290.8 μM for targeted PFCAs, and 41.22 μM to 67.44 μM for targeted PFSAs. The inhibitory effect of PFCAs increased significantly with carbon chain (7–18 carbons), whereas the short chain PFCAs (less than 7 carbons) did not show any effect. Circular dichroism results showed that PFAA binding induced significant protein secondary structural changes. Molecular docking revealed that the inhibitory effect could be rationalized well by the cleft binding mode as well as the size, substituent group and hydrophobic characteristics of the PFAAs. At non-cytotoxic concentrations, three selected PFAAs inhibited LDC activity in HepG2 cells, and subsequently resulted in the decreased cadaverine level in the exposed cells, suggesting that LDC may be a possible target of PFAAs for theirin vivotoxic effects.
