Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/201349
Type: Artigo de periódico
Title: Increase In Ampk Brought About By Cocoa Is Renoprotective In Experimental Diabetes Mellitus By Reducing Nox4/tgfβ-1 Signaling.
Author: Papadimitriou, Alexandros
Peixoto, Elisa B M I
Silva, Kamila C
Lopes de Faria, Jacqueline M
Lopes de Faria, José B
Abstract: The 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.
Subject: Amp-activated Protein Kinases
Animals
Cacao
Diabetes Mellitus, Experimental
Diabetic Nephropathies
Nadph Oxidase
Polyphenols
Rats, Inbred Shr
Transforming Growth Factor Beta1
Up-regulation
5′ Adenosine Monophosphate-activated Protein Kinase (ampk)
Cocoa Enriched With Polyphenols (ch)
Diabetic Nephropathy (dn)
Extracellular Matrix Accumulation (ecm)
Nicotinamide Adenine Dinucleotide Phosphate (nadph) Oxidase
Transforming Growth Factor β-1 (tgfβ-1)
Rights: fechado
Identifier DOI: 10.1016/j.jnutbio.2014.03.010
Address: http://www.ncbi.nlm.nih.gov/pubmed/24768660
Date Issue: 2014
Appears in Collections:Unicamp - Artigos e Outros Documentos

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