Nrf-2 Actives Antioxidant Defense to Protect the Proinflammatory and Oxidative Stress in Mouse MLE-12 Pulmonary Epithelial Cells

摘要

Particulate matter (PM) as a kind of particulate pollution cause proin flammatory with their coating transition metals,quinone,organic carbon (OC),polycyclic aromatic hydrocarbons (PAHs) and etc.It has demonstrated that the biological effect of PM is associated with its oxidation stress to generate reactive oxygen species (ROS).However,the mechanism of PM-induced inflammation and oxidative stress is not fully clear.It has been reported that transcriptional regulation of antioxidant or detoxifying genes is predominantly mediated by a redox-sensitive transcription factor NFE2 related factor-2 (Nrf-2).Nrf-2 is a basic leucine zipper redox-sensitive transcriptional factor that plays a central role in antioxidant response element (ARE)-mediated detoxifying and antioxidant enzymes including reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH),quinone oxid oreductase-1 (NQO1),superoxide dismutase (SOD),glutathione S-transferase (GST),hemeoxygenase-1 (HO-1),and γ-glutamyl cysteine ligase (GCL).In the present study,mouse pulmonary cell MLE-12 cells were treated with 50 μg/mL ambient particles (2.5-10 μm) for 6 h and 12 h.We found that the mRNA expression levels of NQO1,HO-1,and GCLC increased in a time-dependent manner.However,no change in the expression of Nrf-2 mRNA was observed.The result suggested that the increased mRNA level of anti-oxidantive enzymes was mediated by Nrf-2 through its translocation and accumulation in nucleus.Therefore,the activation of Nrf-2-ARE pathway may be a protective response of cells to prevent anti-oxidative effects of particulate matter in vitro.