Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 23, Issue 7, Pages 699-705Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2011.03.012
Keywords
SIRT1; FOXO3a; p47phox; Oxidative stress; Resveratrol and diabetes
Funding
- NIH [K24 AT00596, R33 DK69801]
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Several lines of evidence support a role for oxidative stress in diabetic complications. Diabetic patients have increased O-2(-) production in monocytes. Loss of SIRT1 activity may be associated with metabolic diseases such as diabetes. Several studies have shown that SIRT1 can regulate mammalian FOXO transcription factors through direct binding and/or deacetylation. However, interactions between SIRT1 and FOX() under diabetic conditions are unclear. The phytochemical resveratrol has recently gained attention for its protection against metabolic disease. Resveratrol has been shown to increase mitochondrial function by activating SIRT1. In this study, we tested the protective effect of resveratrol on cellular oxidative stress through the SIRT1-FOXO pathway under high-glucose conditions. Human monocytic (THP-1) cells were cultured in the presence of mannitol (osmolar control) or normoglycemic (NG, 5.5 mmol/l glucose) or hyperglycemic (HG, 25 mmol/l glucose) conditions in absence or presence of resveratrol (3 and 6 mu mol/l) for 48 h. We first examined SIRT1 activity and oxidative stress in monocytes of Type 1 diabetes mellitus (T1DM) patients compared with healthy controls. In T1DM patients, monocytic SIRT1 expression was significantly decreased and p47phox expression was increased compared with controls. Under HG in vitro. SIRT1 and FOXO3a were significantly decreased compared with NG, and this was reversed by resveratrol treatment, concomitant with reduction in HG-induced superoxide production and p47phox. Under HG, SIRT1 small interfering RNA (siRNA) inhibited FOXO3a, and there was no beneficial effect of resveratrol in siRNA-treated HG-induced cells. Thus, resveratrol decreases HG-induced superoxide production via up-regulation of SIRT1, induction of FOXO3a and inhibition of p47phox in monocytes. (C) 2012 Elsevier Inc. All rights reserved.
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