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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Theobromine increases NAD(+)/Sirt-1 activity and protects the kidney under diabetic conditions

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Autor(es):
Papadimitriou, Alexandros [1] ; Silva, Kamila C. [1] ; Peixoto, Elisa B. M. I. [1] ; Borges, Cynthia M. [1] ; Lopes de Faria, Jacqueline M. [1] ; Lopes de Faria, Jose B. [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, UNICAMP, Fac Med Sci, Renal Pathophysiol Lab, Sao Paulo - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY; v. 308, n. 3, p. F209-F225, FEB 1 2015.
Citações Web of Science: 13
Resumo

Reduction in sirtuin 1 (Sirt-1) is associated with extracellular matrix (ECM) accumulation in the diabetic kidney. Theobromine may reduce kidney ECM accumulation in diabetic rats. In the current study, we aimed to unravel, under diabetic conditions, the mechanism of kidney ECM accumulation induced by a reduction in Sirt-1 and the effect of theobromine in these events. In vitro, we used immortalized human mesangial cells (iHMCs) exposed to high glucose (HG; 30 mM), with or without small interfering RNA for NOX4 and Sirt-1. In vivo, spontaneously hypertensive rats (SHR) were rendered diabetic by means of streptozotocin and studied after 12 wk. The effects of treatment with theobromine were investigated under both conditions. HG leads to a decrease in Sirt-1 activity and NAD(+) levels in iHMCs. Sirt-1 activity could be reestablished by treatment with NAD(+), silencing NOX4, and poly (ADP-ribose) polymerase-1 (PARP-1) blockade, or with theobromine. HG also leads to a low AMP/ATP ratio, acetylation of SMAD3, and increased collagen IV, which is prevented by theobromine. Sirt-1 or AMPK blockade abolished these effects of theobromine. In diabetic SHR, theobromine prevented increases in albuminuria and kidney collagen IV, reduced AMPK, elevated NADPH oxidase activity and PARP-1, and reduced NAD(+) levels and Sirt-1 activity. These results suggest that in diabetes mellitus, Sirt-1 activity is reduced by PARP-1 activation and NAD(+) depletion due to low AMPK, which increases NOX4 expression, leading to ECM accumulation mediated by transforming growth factor (TGF)-beta 1 signaling. It is suggested that Sirt-1 activation by theobromine may have therapeutic potential for diabetic nephropathy. (AU)

Processo FAPESP: 12/22452-8 - A teobromina pode estimular SIRT1 (silent information regulator 1) e reduzir o estresse oxidativo e fibrose renal associados ao Diabetes mellitus?
Beneficiário:Jose Butori Lopes de Faria
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 08/57560-0 - Efeitos do chá verde (Camellia sinensis), do cacau e de um doador de óxido nítrico na nefropatia e retinopatia diabética: papel da redução do estresse oxidativo e da inflamação e do aumento do óxido nítrico
Beneficiário:Jose Butori Lopes de Faria
Modalidade de apoio: Auxílio à Pesquisa - Temático