title: The cytotoxic effect of the NOS-mediated oxidative stress in MCF-7 cells after PbCl₂ exposure.
abstract: 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 (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.
authors.affiliation: School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.|School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.|Bor S. Luh Food Safety Research Center, Shanghai, 200240, People's Republic of China.
authors.forename: Lingying
authors.initials: L
authors.lastname: Zhong
authors.affiliation: School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.|Bor S. Luh Food Safety Research Center, Shanghai, 200240, People's Republic of China.|Key Laboratory of Urban Agriculture (South) of Ministry of Agriculture, Shanghai, 200240, People's Republic of China.
authors.forename: Lumei
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.|Bor S. Luh Food Safety Research Center, Shanghai, 200240, People's Republic of China.|Key Laboratory of Urban Agriculture (South) of Ministry of Agriculture, Shanghai, 200240, People's Republic of China.
authors.forename: Lurong
authors.initials: L
authors.lastname: Xu
authors.affiliation: School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.|Bor S. Luh Food Safety Research Center, Shanghai, 200240, People's Republic of China.|Key Laboratory of Urban Agriculture (South) of Ministry of Agriculture, Shanghai, 200240, People's Republic of China.
authors.forename: Qunlu
authors.initials: Q
authors.lastname: Liu
authors.affiliation: School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.|Bor S. Luh Food Safety Research Center, Shanghai, 200240, People's Republic of China.|Key Laboratory of Urban Agriculture (South) of Ministry of Agriculture, Shanghai, 200240, People's Republic of China.|Shanghai Food Safety Engineering Research Center, Shanghai, 200240, People's Republic of China.
authors.forename: Linlei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.|Bor S. Luh Food Safety Research Center, Shanghai, 200240, People's Republic of China.|Key Laboratory of Urban Agriculture (South) of Ministry of Agriculture, Shanghai, 200240, People's Republic of China.
authors.forename: Yuee
authors.initials: Y
authors.lastname: Zhi
authors.affiliation: School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.|Bor S. Luh Food Safety Research Center, Shanghai, 200240, People's Republic of China.|Key Laboratory of Urban Agriculture (South) of Ministry of Agriculture, Shanghai, 200240, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.|Bor S. Luh Food Safety Research Center, Shanghai, 200240, People's Republic of China.|Key Laboratory of Urban Agriculture (South) of Ministry of Agriculture, Shanghai, 200240, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhou
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007854:Lead / Q000633:toxicity*; D061986:MCF-7 Cells; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004785:Environmental Pollutants; D015852:Eukaryotic Initiation Factor-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D007854:Lead; D009569:Nitric Oxide; C029891:lead chloride; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D000111:Acetylcysteine
keywords: heavy metal; lead (Pb); nitric oxide synthase (NOS); oxidative stress; the alpha subunit of eukaryotic initiation factor 2 (elF2α) phosphorylation