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The cytotoxic effect of the NOS ‐mediated oxidative stress in MCF ‐7 cells after P b C l 2 exposure
Author(s) -
Zhong Lingying,
Wang Lumei,
Xu Lurong,
Liu Qunlu,
Jiang Linlei,
Zhi Yuee,
Lu Wei,
Zhou Pei
Publication year - 2016
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22073
Subject(s) - nitric oxide , cytotoxicity , nitric oxide synthase , oxidative stress , reactive oxygen species , enos , chemistry , phosphorylation , endothelial nos , biochemistry , signal transduction , microbiology and biotechnology , biology , in vitro , organic chemistry
The potential Pb‐induced cytotoxicity in various tissues and biological systems has been reported. Some evidences also indicate that the Pb‐caused cytotoxicity may be associated with the nitric oxide synthase (NOS). However, there remains uncertainty about the role of the NOS signaling pathway during the Pb‐induced cytotoxicity. In this report, we provide data showing that PbCl 2 treatment depresses the expressions of the three distinct NOS isoforms: neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) on both transcriptional and translational levels in MCF‐7 cells. The down‐regulation of NOSs expressions by PbCl 2 exposure leads to reduced NOS activity and nitric oxide (NO) production. Meanwhile, the intracellular reactive oxygen species (ROS) level is elevated after PbCl 2 exposure, which leads to the alpha subunit of eukaryotic initiation factor 2 (elF2α) phosphorylation. The reduction effects of the free radical scavenger N ‐acetyl‐ l ‐cysteine or the NOS substrate l ‐arginine on the Pb‐induced ROS generation suggest that the NOS signaling pathway plays a key role in the Pb‐induced oxidative stress, which further results in the elF2α phosphorylation and cytotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 601–608, 2016.