Tropospheric ozone affects SRB1 levels via oxidative post-translational modifications in lung cells

Claudia Sticozzi, Alessandra Pecorelli, Arianna Romani, Giuseppe Belmonte, Franco Cervellati, Emanuela Maioli, Mary Ann Lila, Carlo Cervellati, Giuseppe Valacchi

Research output: Contribution to journalArticle

Abstract

Exposure to air pollution is associated with increased respiratory morbidities and susceptibility to lung dysfunction. Ozone (O3) is commonly recognized as one of the most noxious air pollutant and has been associated with several lung pathologies. It has been demonstrated that decreased lung disorder severity and incidence are connected with the consumption of a diet rich in fruits and vegetables, suggesting that higher intake of dietary micronutrients and phytoactive compounds can be beneficial. However, dietary supplementation - i.e. vitamin E (α-tocopherol) or vitamin A - has not always been effective in improving pulmonary function. Recently, research on the role of nutritional antioxidants on human health has focused more on studying their uptake at the cellular level rather than their effective ability to scavenge reactvive oxygen species (ROS). The Scavenger Receptor B1 (SRB1) has been shown to play a prominent role in the uptake, delivery and regulation of vitamin E in the lung. Given the importance of SRB1 in maintaining lung tissue in a healthy condition, we hypothesize that its expression could be modulated by pollution exposure, which thus could indirectly affect the uptake and/or delivery of lipophilic substances, such as vitamin E. To characterize the molecular mechanism involved in the redox modulation of SRB1, its cellular levels were assessed in human alveolar epithelial cells after O3 exposure. The results demonstrated that O3 induced the loss of SRB1 protein levels. This decline seems to be driven by hydrogen peroxide (H2O2) as a consequence of an increased activation of cellular NADPH oxidase (NOX), as demonstrated by the use of NOX inhibitors or catalase that reversed this effect. Furthermore, O3 caused the formation of SRB1-aldheyde adducts (4-hydroxy-2-nonenal) and the consequent increase of its ubiquitination, a mechanism that could account for SRB1 protein loss.

Original languageEnglish (US)
Pages (from-to)287-295
Number of pages9
JournalFree Radical Biology and Medicine
Volume126
DOIs
StatePublished - Oct 2018

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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    Sticozzi, C., Pecorelli, A., Romani, A., Belmonte, G., Cervellati, F., Maioli, E., Lila, M. A., Cervellati, C., & Valacchi, G. (2018). Tropospheric ozone affects SRB1 levels via oxidative post-translational modifications in lung cells. Free Radical Biology and Medicine, 126, 287-295. https://doi.org/10.1016/j.freeradbiomed.2018.07.007