title: All-trans retinoic acid prevents oxidative stress-induced loss of renal tight junction proteins in type-1 diabetic model.
abstract: We previously reported that diabetes decreased the expression of renal tight junction (TJ) proteins claudin-5 in glomerulus, and claudin-2 and occludin in proximal tubule through an oxidative stress dependent way. Now we investigated whether all-trans retinoic acid (atRA), a compound that plays a relevant role in kidney maintenance and that possesses antioxidant properties, prevents loss of TJ proteins in streptozotocin (STZ)-treated rats. atRA was administered daily by gavage (1mg/kg) from Days 3-21 after STZ administration. atRA attenuated loss of body weight, proteinuria and natriuresis but it did not prevent hyperglucemia. Other metabolic alterations, such as: increased kidney injury molecule (KIM)-1, oxidative stress, protein kinase C (PKC) beta 2, NADPH oxidase subunits (p47(phox) and gp91(phox)) expressions and endothelial nitric oxide synthase (eNOS) uncoupling, and decreased nitric oxide synthesis, nuclear factor-erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions were also attenuated by atRA. In vitro scavenging capacity assays showed that atRA scavenged peroxyl radicals (ROO•), singlet oxygen ((1)O2) and hypochlorous acid (HOCl) in a concentration-dependent manner. Decreased expressions of occludin, claudins-2 and -5 induced by diabetes were ameliorated by atRA. We also found that diabetes induced tyrosine nitration (3-NT), SUMOylation and phosphorylation in serine residues of claudin-2 and atRA prevented these changes. In conclusion, atRA exerted nephroprotective effects by attenuating oxidative stress and preventing loss of renal TJ proteins.
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), México D.F., 07360, Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Molina-Jijón
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), México D.F., 07360, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rodríguez-Muñoz
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), México D.F., 07360, Mexico.
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Namorado
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), México D.F., 07360, Mexico.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bautista-García
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), 04510 University City D.F., Mexico.
authors.forename: Omar Noel
authors.initials: ON
authors.lastname: Medina-Campos
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), 04510 University City D.F., Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), México D.F., 07360, Mexico. Electronic address: jreyes@fisio.cinvestav.mx.
authors.forename: José L
authors.initials: JL
authors.lastname: Reyes
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D007668:Kidney / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D062725:Tight Junction Proteins / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D062725:Tight Junction Proteins; D014212:Tretinoin
keywords: All-trans retinoic acid; Claudins; Diabetes; Oxidative stress; Renal tight junctions