Endocytosis Of Tight Junctions Caveolin Nitrosylation Dependent Is Improved By Cocoa Via Opioid Receptor On Rpe Cells In Diabetic Conditions.

dc.creatorRosales, Mariana Aparecida B
dc.creatorSilva, Kamila Cristina
dc.creatorDuarte, Diego A
dc.creatorRossato, Franco Aparecido
dc.creatorLopes de Faria, José B
dc.creatorLopes de Faria, Jacqueline M
dc.date2014-Sep
dc.date2015-11-27T13:43:18Z
dc.date2015-11-27T13:43:18Z
dc.date.accessioned2018-03-29T01:21:54Z
dc.date.available2018-03-29T01:21:54Z
dc.identifierInvestigative Ophthalmology & Visual Science. v. 55, n. 9, p. 6090-100, 2014-Sep.
dc.identifier1552-5783
dc.identifier10.1167/iovs.14-14234
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/25190662
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/201693
dc.identifier25190662
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1301926
dc.descriptionRetinal 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.
dc.description55
dc.description6090-100
dc.languageeng
dc.relationInvestigative Ophthalmology & Visual Science
dc.relationInvest. Ophthalmol. Vis. Sci.
dc.rightsfechado
dc.rightsCopyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
dc.sourcePubMed
dc.subjectAnimals
dc.subjectBlood-retinal Barrier
dc.subjectBlotting, Western
dc.subjectCacao
dc.subjectCaveolin 1
dc.subjectCell Line
dc.subjectClaudin-1
dc.subjectDextrans
dc.subjectElectric Impedance
dc.subjectEndocytosis
dc.subjectFluorescent Antibody Technique, Indirect
dc.subjectGlucose
dc.subjectHumans
dc.subjectNitric Oxide Synthase Type Ii
dc.subjectNitrosation
dc.subjectOccludin
dc.subjectPermeability
dc.subjectPolyphenols
dc.subjectReactive Oxygen Species
dc.subjectReceptors, Opioid
dc.subjectRetinal Pigment Epithelium
dc.subjectSwine
dc.subjectTight Junctions
dc.subjectTumor Necrosis Factor-alpha
dc.subjectRpe
dc.subjectCocoa
dc.subjectHigh Glucose
dc.subjectNitrosative Stress
dc.subjectTight Junction
dc.titleEndocytosis Of Tight Junctions Caveolin Nitrosylation Dependent Is Improved By Cocoa Via Opioid Receptor On Rpe Cells In Diabetic Conditions.
dc.typeArtículos de revistas


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