Istvan Arany1, Tibor Fülöp2,3, Mehul Dixit4. 1. Division of Pediatric Nephrology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, U.S.A. iarany@umc.edu. 2. Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC, U.S.A. 3. Medical Services, Ralph H. Johnson VA Medical Center, Charleston, SC, U.S.A. 4. Division of Pediatric Nephrology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, U.S.A.
Abstract
BACKGROUND/AIM: We have previously reported that simvastatin exhibits antioxidant properties via extracellular signal-regulated kinase (ERK)/cAMP-response element binding (CREB) protein-dependent induction of heme oxygenase-1 (HO1) and chronic nicotine exposure inhibits ERK/CREB signaling in renal proximal tubule cells (through p66shc). Herein, whether nicotine dampens simvastatin-dependent HO1 induction was determined. MATERIALS AND METHODS: Renal proximal tubule (NRK52E) cells were pre-treated with 200 μM nicotine for 24 h followed by 10 μM simvastatin. Promoter activity of HO1 and manganese superoxide dismutase (MnSOD) and activation of CREB and ERK (via ELK1) were determined in luciferase reporter assays. CREB and p66shc were modulated via genetic means. RESULTS: Nicotine suppressed simvastatin-dependent activation of HO1 and MnSOD promoters and activity of CREB and ELK1 via p66shc. Overexpression of CREB or knockdown of p66shc restored simvastatin-dependent induction of HO1 and MnSOD in the presence of nicotine. CONCLUSION: Antioxidant efficiency of simvastatin might be significantly lessened in smokers/E-cigarette users. Copyright
BACKGROUND/AIM: We have previously reported that simvastatin exhibits antioxidant properties via extracellular signal-regulated kinase (ERK)/cAMP-response element binding (CREB) protein-dependent induction of heme oxygenase-1 (HO1) and chronic nicotine exposure inhibits ERK/CREB signaling in renal proximal tubule cells (through p66shc). Herein, whether nicotine dampens simvastatin-dependent HO1 induction was determined. MATERIALS AND METHODS: Renal proximal tubule (NRK52E) cells were pre-treated with 200 μM nicotine for 24 h followed by 10 μM simvastatin. Promoter activity of HO1 and manganese superoxide dismutase (MnSOD) and activation of CREB and ERK (via ELK1) were determined in luciferase reporter assays. CREB and p66shc were modulated via genetic means. RESULTS:Nicotine suppressed simvastatin-dependent activation of HO1 and MnSOD promoters and activity of CREB and ELK1 via p66shc. Overexpression of CREB or knockdown of p66shc restored simvastatin-dependent induction of HO1 and MnSOD in the presence of nicotine. CONCLUSION: Antioxidant efficiency of simvastatin might be significantly lessened in smokers/E-cigarette users. Copyright
Authors: E Migliaccio; S Mele; A E Salcini; G Pelicci; K M Lai; G Superti-Furga; T Pawson; P P Di Fiore; L Lanfrancone; P G Pelicci Journal: EMBO J Date: 1997-02-17 Impact factor: 11.598
Authors: Patrick M Honore; Rita Jacobs; Inne Hendrickx; Elisabeth De Waele; Viola Van Gorp; Jouke De Regt; Herbert D Spapen Journal: Blood Purif Date: 2016-12-13 Impact factor: 2.614
Authors: Victoria Cachofeiro; Marian Goicochea; Soledad García de Vinuesa; Pilar Oubiña; Vicente Lahera; José Luño Journal: Kidney Int Suppl Date: 2008-12 Impact factor: 10.545