Theobromine increases NAD+/Sirt1 activity and protects the kidney under diabetic conditions.

Theobromine increases NAD+/Sirt1 activity and protects the kidney under diabetic conditions. Am J Physiol Renal Physiol. 2014 Nov 19;:ajprenal.00252.2014 Authors: Papadimitriou A, Silva KC, Peixoto EB, Borges CM, Lopes de Faria JM, Lopes de Faria JB Abstract 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 Sirt1. In vivo, spontaneously hypertensive rats (SHR) were rendered diabetic by means of streptozotocin and studied after 12 weeks. 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 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 rats, theobromine prevented increases ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research