Increase In Ampk Brought About By Cocoa Is Renoprotective In Experimental Diabetes Mellitus By Reducing Nox4/tgfβ-1 Signaling.

dc.creatorPapadimitriou, Alexandros
dc.creatorPeixoto, Elisa B M I
dc.creatorSilva, Kamila C
dc.creatorLopes de Faria, Jacqueline M
dc.creatorLopes de Faria, José B
dc.date2014-Jul
dc.date2015-11-27T13:42:25Z
dc.date2015-11-27T13:42:25Z
dc.date.accessioned2018-03-29T01:20:35Z
dc.date.available2018-03-29T01:20:35Z
dc.identifierThe Journal Of Nutritional Biochemistry. v. 25, n. 7, p. 773-84, 2014-Jul.
dc.identifier1873-4847
dc.identifier10.1016/j.jnutbio.2014.03.010
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/24768660
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/201349
dc.identifier24768660
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1301582
dc.descriptionThe aims of the present study were to investigate, in diabetes mellitus (DM), the mechanism of NOX4 up-regulation, its link with 5' adenosine monophosphate-activated protein kinase (AMPK) inactivation and transforming growth factor (TGF) ß-1 signaling in determining the accumulation of kidney extracellular matrix (ECM), and the possible action of cocoa enriched with polyphenols (CH) in these events. After 16 weeks of DM, spontaneously hypertensive rats showed increased kidney TGFβ-1 levels and expression of phosphorylated smad2, collagen IV and fibronectin in parallel with elevated NOX4 expression and reduced phosphorylated AMPK. CH treatment in diabetic rats prevented all of these abnormalities. In immortalized human mesangial cells exposed to high glucose (HG), or TGFβ-1, CH, nicotinamide adenine dinucleotide phosphate blocker, or silencing NOX4 ameliorated enhanced phosphorylated smad2 and collagen IV. Reduction in phosphorylated AMPK induced by HG or TGFβ-1 was ameliorated by CH or activation of AMPK, which reduced phosphorylation of smad2 and collagen IV via reduction in NOX4 expression. The effects of CH were abolished by AMPK blockade. These results suggest that inactivation in AMPK leads to NOX4 up-regulation, activation of TGFβ-1 signaling and increased ECM accumulation. Additionally, increased TGF-ß1 per se leads to the amplification of ECM production by reducing AMPK and promoting the activation of NOX4. It is suggested that the activation of AMPK by CH followed by reduction in NOX4/TGFβ-1 signaling may have a therapeutic potential in diabetic nephropathy.
dc.description25
dc.description773-84
dc.languageeng
dc.relationThe Journal Of Nutritional Biochemistry
dc.relationJ. Nutr. Biochem.
dc.rightsfechado
dc.rightsCrown Copyright © 2014. Published by Elsevier Inc. All rights reserved.
dc.sourcePubMed
dc.subjectAmp-activated Protein Kinases
dc.subjectAnimals
dc.subjectCacao
dc.subjectDiabetes Mellitus, Experimental
dc.subjectDiabetic Nephropathies
dc.subjectNadph Oxidase
dc.subjectPolyphenols
dc.subjectRats, Inbred Shr
dc.subjectTransforming Growth Factor Beta1
dc.subjectUp-regulation
dc.subject5′ Adenosine Monophosphate-activated Protein Kinase (ampk)
dc.subjectCocoa Enriched With Polyphenols (ch)
dc.subjectDiabetic Nephropathy (dn)
dc.subjectExtracellular Matrix Accumulation (ecm)
dc.subjectNicotinamide Adenine Dinucleotide Phosphate (nadph) Oxidase
dc.subjectTransforming Growth Factor β-1 (tgfβ-1)
dc.titleIncrease In Ampk Brought About By Cocoa Is Renoprotective In Experimental Diabetes Mellitus By Reducing Nox4/tgfβ-1 Signaling.
dc.typeArtículos de revistas


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