Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 26, Issue 5, Pages 441-454Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2014.11.018
Keywords
Diabetes; Renal tight junctions; Oxidative stress; All-trans retinoic acid; Claudins
Funding
- Consejo Nacional de Ciencia y Tecnologia (CONACyT), Mexico [0179870, 224642, IN210713, 255413]
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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 (1 mg/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 factoretythroid-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 center dot), singlet oxygen (O-1(2)) and hypochlorous acid (HOC1) 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. (C) 2015 Elsevier Inc. All rights reserved.
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