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Resveratrol upregulates SIRT1 and inhibits cellular oxidative stress in the diabetic milieu: mechanistic insights
Author(s) -
Devaraj Sridevi,
Yun JungMi,
Jialal Ishwarlal
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.224.5
Subject(s) - resveratrol , oxidative stress , sirtuin 1 , chemistry , downregulation and upregulation , superoxide , pharmacology , endocrinology , diabetes mellitus , medicine , biochemistry , biology , enzyme , gene
Oxidative stress is pivotal in diabetic complications. Loss of SIRT1 activity may be associated with diabetes. SIRT1 can regulate FOXO transcription. However, interactions between SIRT1 and FOXO under diabetic conditions are unclear. In T1DM patients, monocytic SIRT1 expression was significantly decreased and p47phox expression was increased compared to controls. The phytochemical resveratrol, increases mitochondrial function by activating SIRT1. We tested the effect of resveratrol on cellular oxidation via the SIRT1‐FOXO pathway under high‐glucose conditions. Human monocytic cells were cultured in presence of mannitol or normo‐ (NG, 5.5 mmol/L glucose) or hyperglycemic (HG, 25 mmol/L glucose) conditions in absence or presence of resveratrol (3 ìmol/L) for 48 h. Under HG in vitro, SIRT1 and FOXO3a were significantly decreased compared to NG, this was reversed by resveratrol, concomitant with reduction in HG‐induced superoxide production and p47phox. SIRT1 siRNA, inhibited HG‐induced FOXO3a and p47phox expression with no additive effect of resveratrol. Thus, resveratrol decreases HG‐induced superoxide production via upregulation of SIRT1, induction of FOXO3a and inhibition of p47phox in monocytes.