Acrolein causes transcriptional induction of phase II genes by activation of Nrf2 in human lung type II epithelial (A549) cells.

摘要: Abstract Acrolein, an α,β-unsaturated aldehyde, is by far the strongest electrophile present in cigarette smoke which involved several lung pathophysiological conditions. Acrolein depletes glutathione and creates thiol imbalance. due to imbalance as well covalent modification of cysteine known inhibit activity redox sensitive transcription factors such NF-κB AP-1. Exposure human type II epithelial (A549) cells non-lethal dose acrolein (150 fmol/cell for 1 h) 80% intracellular increases γ-glutamylcysteine synthetase (γ-GCS) at 6–12 h post-treatment, helps replenishing normal level. treatment activates phase genes general, indicated increase mRNA NAD (P) H:quinone oxidoreductase (NQO1). Western blot analysis revealed increased level factor, Nrf2 nuclear extract from treated cells. Electrophoretic mobility shift assay shows binding proteins antioxidant response element (ARE) consensus sequence after with acrolein. The involvement ARE mediated transcriptional activation exposure has been confirmed NQO1-ARE reporter assay. ability transcriptionaly activate responsible enzymes may form basis resistance against cell death can have implications related carcinogenesis.