Overexpression of SIRT1 protects pancreatic beta-cells against cytokine toxicity by suppressing the nuclear factor-kappaB signaling pathway.

ABSTRACT:

Objective

SIRT1, a class III histone/protein deacetylase, is known to interfere with the nuclear factor-kappaB (NF-kappaB) signaling pathway and thereby has an anti-inflammatory function. Because of the central role of NF-kappaB in cytokine-mediated pancreatic beta-cell damage, we postulated that SIRT1 might work in pancreatic beta-cell damage models.

Research design and methods

RINm5F (RIN) cells or isolated rat islets were treated with interleukin-1beta and interferon-gamma. SIRT1 was activated by resveratrol, a pharmacological activator, or ectopic overexpression. The underlying mechanisms of SIRT1 against cytokine toxicity were further explored.

Results

Treatment of RIN cells with cytokines induced cell damage, and this damage was well correlated with the expressi

SUBMITTER: Lee JH 

PROVIDER: S-EPMC2628607 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature