title: α-Tocopherol protects renal cells from nicotine- or oleic acid-provoked oxidative stress via inducing heme oxygenase-1.
abstract: Smoking and obesity increases renal oxidative stress via nicotine (NIC) or free fatty acid such as oleic acid (OA) but decreases levels of the vitamin E-derivative α-tocopherol (TOC), which has shown to stimulate the antioxidant system such as heme oxygenase-1 (HO-1). Hence, we hypothesized that supplementation of TOC may protect renal proximal tubules from NIC- or OA-mediated oxidative stress by upregulating the HO-1 gene. NIC- or OA-dependent production of reactive oxygen species (ROS) was determined in the presence or absence of various pharmacologic or genetic inhibitors that modulate HO-1 activation and enhancer elements in the HO-1 promoter such as the antioxidant response element (ARE) and the cAMP-response element (CRE) in renal proximal tubule cells (NRK52E). Activity of the HO-1 promoter, the ARE and the CRE was determined in luciferase assays. We found that pre- or posttreatment with TOC attenuated NIC- or OA-dependent ROS production that required HO-1 activation. TOC activated the HO-1 promoter via the CRE but not the ARE enhancer through the extracellular signal-regulated kinase (ERK) and protein kinase A (PKA). Consequently, inhibitors of ERK, PKA, or CRE activation mitigated beneficial effects of TOC on NIC- or OA-mediated ROS production. Hence, vitamin E supplementation-via induction of the cytoprotective HO-1-may help to reduce renal oxidative stress imposed by smoking or obesity.
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Dustin K
authors.initials: DK
authors.lastname: Reed
authors.forename: Samuel
authors.initials: S
authors.lastname: Hall
authors.forename: Istvan
authors.initials: I
authors.lastname: Arany
mesh_terms: D000818:Animals; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004790:Enzyme Induction; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D019301:Oleic Acid / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D017382:Reactive Oxygen Species; D019301:Oleic Acid; D009538:Nicotine; D051547:Heme Oxygenase-1; D011494:Protein Kinases; D024502:alpha-Tocopherol