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Type: Artigo de periódico
Title: Endocytosis Of Tight Junctions Caveolin Nitrosylation Dependent Is Improved By Cocoa Via Opioid Receptor On Rpe Cells In Diabetic Conditions.
Author: Rosales, Mariana Aparecida B
Silva, Kamila Cristina
Duarte, Diego A
Rossato, Franco Aparecido
Lopes de Faria, José B
Lopes de Faria, Jacqueline M
Abstract: Retinal pigment epithelium cells, along with tight junction (TJ) proteins, constitute the outer blood retinal barrier (BRB). Contradictory findings suggest a role for the outer BRB in the pathogenesis of diabetic retinopathy (DR). The aim of this study was to investigate whether the mechanisms involved in these alterations are sensitive to nitrosative stress, and if cocoa or epicatechin (EC) protects from this damage under diabetic (DM) milieu conditions. Cells of a human RPE line (ARPE-19) were exposed to high-glucose (HG) conditions for 24 hours in the presence or absence of cocoa powder containing 0.5% or 60.5% polyphenol (low-polyphenol cocoa [LPC] and high-polyphenol cocoa [HPC], respectively). Exposure to HG decreased claudin-1 and occludin TJ expressions and increased extracellular matrix accumulation (ECM), whereas levels of TNF-α and inducible nitric oxide synthase (iNOS) were upregulated, accompanied by increased nitric oxide levels. This nitrosative stress resulted in S-nitrosylation of caveolin-1 (CAV-1), which in turn increased CAV-1 traffic and its interactions with claudin-1 and occludin. This cascade was inhibited by treatment with HPC or EC through δ-opioid receptor (DOR) binding and stimulation, thereby decreasing TNF-α-induced iNOS upregulation and CAV-1 endocytosis. The TJ functions were restored, leading to prevention of paracellular permeability, restoration of resistance of the ARPE-19 monolayer, and decreased ECM accumulation. The detrimental effects on TJs in ARPE-19 cells exposed to DM milieu occur through a CAV-1 S-nitrosylation-dependent endocytosis mechanism. High-polyphenol cocoa or EC exerts protective effects through DOR stimulation.
Subject: Animals
Blood-retinal Barrier
Blotting, Western
Caveolin 1
Cell Line
Electric Impedance
Fluorescent Antibody Technique, Indirect
Nitric Oxide Synthase Type Ii
Reactive Oxygen Species
Receptors, Opioid
Retinal Pigment Epithelium
Tight Junctions
Tumor Necrosis Factor-alpha
High Glucose
Nitrosative Stress
Tight Junction
Citation: Investigative Ophthalmology & Visual Science. v. 55, n. 9, p. 6090-100, 2014-Sep.
Rights: fechado
Identifier DOI: 10.1167/iovs.14-14234
Date Issue: 2014
Appears in Collections:Unicamp - Artigos e Outros Documentos

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