Role of statins and mevalonate pathway on impaired HDAC2 activity induced by oxidative stress in human airway epithelial cells

European Journal of Pharmacology
Maria Gabriella MateraBarbara Rinaldi

Abstract

In patients with chronic obstructive pulmonary disease (COPD) the inflammatory response is often steroid-resistant, likely since oxidative stress and cigarette smoking impair histone deacetylase 2 (HDAC2) activity. Since it has been demonstrated that statins may restore the HDAC2 activity in cultured human endothelial cells, the aim of this study was to investigate the effects of statins in reversing the steroid-resistance induced by oxidative stress. We evaluated the effects of simvastatin and dexamethasone on HDAC2 expression and activity, and the role of mevalonate and Rho/ROCK pathways in A549 cells, a human lung type II epithelial cell line stressed with H2O2. Our results documented that H2O2 significantly reduced the HDAC2 expression and activity. In H2O2 treated cells dexamethasone was unable to restore the activity of HDAC2, whereas simvastatin restored both the expression and the activity of this enzyme. Our data also showed that mevalonate reduced the activity of HDAC2 whereas Y27632, a Rho/ROCK inhibitor, had no effect on HDAC2 activity when co-administered with simvastatin. Our data suggest that statins could have the potential to restore corticosteroid sensitivity in A549 cells. The evidences of this study suggest ...Continue Reading

Citations

Nov 13, 2018·Current Opinion in Pulmonary Medicine·Diana E Amariei, Robert M Reed
Aug 28, 2020·European Journal of Clinical Investigation·Nooshin MohammadzadehAmirhossein Sahebkar
Aug 8, 2019·Multidisciplinary Respiratory Medicine·Paola RoglianiMaria Gabriella Matera

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