title: The role of nitric oxide synthase in an early phase Cd-induced acute cytotoxicity in MCF-7 cells.
abstract: Literature to date has confirmed that cadmium (Cd) can accomplish its toxic effects via the free radical-induced damage, but Cd itself cannot generate free radicals directly. Nitric oxide (NO) is a fundamental molecule that interplays with reactive oxygen species (ROS), which may be associated with the Cd-induced cytotoxicity. However, the role of nitric oxide synthase (NOS) in an early phase Cd-induced acute cytotoxicity and its interaction has not been studied. In this report, we provide data showing that CdCl2 (10 μM, 100 μM, 1 mM) could modulate NOS activity in terms of NO production which was first suppressed with the release of Ca(2+) and Zn(2+), then induced with the transcriptional and translational activation of the three NOS isoforms in a possible feedback manner. The ROS level in cells was increased after CdCl2 exposure. By using the free radical scavenger N-acetyl-L-cysteine (LNAC) or the NOS activity inhibitor N(G)-methyl-L-arginine (LNMMA), it was demonstrated that NOS played a critical role on the Cd-induced ROS generation. The Cd-induced cytotoxicity was associated with the NOS-mediated oxidative stress in MCF-7 cells.
authors.affiliation: School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
authors.forename: Lingying
authors.initials: L
authors.lastname: Zhong
authors.forename: Lumei
authors.initials: L
authors.lastname: Wang
authors.forename: Lurong
authors.initials: L
authors.lastname: Xu
authors.forename: Qunlu
authors.initials: Q
authors.lastname: Liu
authors.forename: Linlei
authors.initials: L
authors.lastname: Jiang
authors.forename: Yuee
authors.initials: Y
authors.lastname: Zhi
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Pei
authors.initials: P
authors.lastname: Zhou
mesh_terms: D002104:Cadmium / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D002104:Cadmium; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase