Reactive sulfur species are involved in cigarette smoke-induced cellular senescence

Rationale: Reactive sulfer species have been recently identified as much stronger antioxidants than glutathione and we have demonstrated that the levels of reactive persulfides/polysulfides are decreased in the lungs of COPD. However, the roles of reactive persulfides/polysulfides in the pathogenesis of COPD remain unclear. The aim of this study was to investigate the role of reactive sulfer species in cigarette smoke (CS)-induced premature senescence in lung resident cells. Methods: Human fetal lung fibroblasts (HFL-1) transfected with siRNA for the novel synthetase of reactive sulfer species were exposed to cigarette smoke extract (CSE). The amount of reactive persulfides/polysulfides was measured using sulfane sulfur probe-4 (SSP-4), a specific probe for reactive sulfer species. The expressions of p53 and p21, markers for senescence, in the cells were analyzed by western blotting. Senescence associated beta galactosidase (SA-β gal) activity was measured using a commercial kit. The release of IL-6 and IL-8, cytokines associated with senescence, were quantified by ELISA. Results: The expression of the synthetase and the SSP-4 level were reduced in the CSE-treated cells. The productions of markers and cytokines associated with senescence were potentiated in the synthetase knockdown CSE-exposed cells compared to the control-siRNA transfected CSE-exposed cells. The SA-β gal activities were significantly augmented in the synthetase knockdown CSE-exposed cells compared to the control-siRNA transfected CSE-exposed cells. Conclusions: The current study suggests that the reduction in reactive sulfer species might be related to CS-induced cellular senescence.