RT Journal Article
SR Electronic
T1 Chronic Nicotine Exposure Reduces Antioxidant Function of Simvastatin in Renal Proximal Tubule Cells
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 1033
OP 1037
DO 10.21873/invivo.11343
VO 32
IS 5
A1 ARANY, ISTVAN
A1 FÜLÖP, TIBOR
A1 DIXIT, MEHUL
YR 2018
UL http://iv.iiarjournals.org/content/32/5/1033.abstract
AB 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.