The cytotoxic effect of the NOS-mediated oxidative stress in MCF-7 cells after PbCl2 exposure

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• 作者：Lingying Zhong ; Lumei Wang ; Lurong Xu ; Qunlu Liu ; Linlei Jiang ; Yuee Zhi ; Wei Lu and Pei Zhou
• 关键词：heavy metal ; lead (Pb) ; nitric oxide synthase (NOS) ; oxidative stress ; the alpha subunit of eukaryotic initiation factor 2 (elF2) phosphorylation
• 刊名：Environmental Toxicology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：31
• 期：5
• 页码：601-608
• 全文大小：375K
• ISSN：1522-7278

文摘

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 PbCl₂ 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 PbCl₂ exposure leads to reduced NOS activity and nitric oxide (NO) production. Meanwhile, the intracellular reactive oxygen species (ROS) level is elevated after PbCl₂ exposure, which leads to the alpha subunit of eukaryotic initiation factor 2 (elF2) 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 elF2 phosphorylation and cytotoxicity.