Aging and oxidative stress affect lung vitamin E tissue uptake

Despite the physiological importance of alpha-tocopherol (a-Toc), the molecular mechanisms involved in maintaining cellular tocopherol levels remain ill-defined. Scavenger receptor B1 (SR-B1) one of large family of scavenger receptors has been shown to mediate a-Toc transfer from HDL via apo A-1 mediated binding to the cells and to be important in the delivery of a-Toc to the tissues. Lung is the main target tissue of gaseous stressors such as O3 and cigarette smoke (CS). Aging and environmental pollution likely affect lung a-Toc content. We assessed the effects of two environmental stressors O3 (0.25 ppm 6 hr per day) and CS (60 mg/m3 6 hr per day) for 4 days on lung tissue from both young and aged mice. a-Toc concentrations in the plasma was significantly higher in the old animal while lung a-Toc was higher in the young group and this effect was inversely correlated with SRB1 levels. Acute exposure to either O3 or CS induced declines in lung SR-B1 levels in all groups. Conversely, lung ABCA1 had an opposite trend. To further characterize the molecular mechanism(s) of SR-B1 modulation by CS, human airway epitheliall cells (A549) were exposed to CS and SR-B1 distribution was assessed. Using immunoblotting, immunoprecipitation, RT-PCR, and confocal microscopy we have demonstrated that the translocation and the consecutive lost of SR-B1 in A549 cells after CS exposure is driven by hydrogen peroxide (H2O2) which derives not only from the CS gas phase but mainly from the activation of cellular NADPH oxidase (NOX). This effect was reversed when the cells were pretreated with NOX inhibitors, catalase, or superoxide dismutase (SOD) inhibitor. Furthermore, CS caused the formation of SRB1-aldheydes adducts (Acrolein and 4-Hydroxynonenal) and the increased of its ubiquitination which is the cause of its degradation. In conclusion, exposure to CS, through the production of H2O2, induced post-translational modifications of SRB1 with the consequence lost of the receptor and this may affect cellular uptake and therefore the cellular content of aTocoiferol