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.

PM2.5 exposure induces vascular dysfunction via NO generated by iNOS in lung of ApoE-/- mouse

“…PM2.5 exposure may activate iNOS via reducing its DNA methylation PM2.5 collected from Oct. to Dec. 2015 in Beijing city was analysed, and PM2.5-adsorbed metal elements and polycyclic aromatic hydrocarbons (PAH) were shown in Table 3. Among these components of the PM2.5 in our study, Zn, Ni, Al, Pb and PAHs were all reported to activate iNOS directly [28][29][30][31][32], suggesting the direct activation of iNOS by these PM2.5 components. Especially, PAHs were verified to upregulate iNOS expression via the decrease of their DNA methylation level [33][34][35].…”