All-trans retinoic acid prevents oxidative stress-induced loss of renal tight junction proteins in type-1 diabetic model

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 re...

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Published in:The Journal of nutritional biochemistry 2015-05, Vol.26 (5), p.441-454
Main Authors: Molina-Jijón, Eduardo, Rodríguez-Muñoz, Rafael, Namorado, María del Carmen, Bautista-García, Pablo, Medina-Campos, Omar Noel, Pedraza-Chaverri, José, Reyes, José L.
Format: Article
Language:English
Subjects:
All-trans retinoic acid
Animals
Claudins
Diabetes
Diabetes Mellitus, Type 1 - metabolism
Female
Kidney - drug effects
Oxidative stress
Oxidative Stress - drug effects
Rats
Rats, Wistar
Renal tight junctions
Tight Junction Proteins - metabolism
Tretinoin - pharmacology
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Summary: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 (p47phox and gp91phox) 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 (1O2) 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.
ISSN:0955-2863
1873-4847
DOI:10.1016/j.jnutbio.2014.11.018