α-Tocopherol protects renal cells from nicotine- or oleic acid-provoked oxidative stress via inducing heme oxygenase-1

• Autores: Dustin K. Reed, Samuel Hall, Istvan Arany
• Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 71, Nº. 1, 2015, págs. 1-7
• Idioma: inglés
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• Resumen

  • 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.