The NAD-dependent histone deacetylase Sirt1 antagonizes p53 transcriptional activity to regulate cell-cycle progression and apoptosis. We have identified a ubiquitin-specific peptidase, USP22, one of the 11 death-from-cancer signature genes that are critical in controlling cell growth and death, as a positive regulator of Sirt1. USP22 interacts with and stabilizes Sirt1 by removing polyubiquiti...

The NAD+-dependent protein deacetylase SIRT1 regulates energy metabolism, responses to stress, and aging by deacetylating many different proteins, including histones and transcription factors. The mechanisms controlling SIRT1 enzymatic activity are complex and incompletely characterized, yet essential for understanding how to develop therapeutics that target SIRT1. Here, we demonstrate that the...

Our previous studies have shown that hyperbaric oxygen preconditioning (HBO-PC) induces tolerance to cerebral ischemia/reperfusion (I/R). This study aimed to investigate whether SirT1, a class III histone deacetylase, is involved in neuroprotection elicited by HBO-PC in animal and cell culture models of ischemia. Rats were subjected to middle cerebral artery occlusion for 120 minutes after HBO-...

Background—Silent information regulator 1 (Sirt1), a class III histone deacetylase, retards aging and protects the heart from oxidative stress. We here examined whether Sirt1 is protective against myocardial ischemia/reperfusion (I/R). Methods and Results—Protein and mRNA expression of Sirt1 is significantly reduced by I/R. Cardiac-specific Sirt1 Ϫ/Ϫ mice exhibited a significant increase (44Ϯ5%...

BRCA mutations are the main known hereditary factors for ovarian cancer. Notably, emerging evidence has led to considerable interest in the role of sirtuin 1 (SIRT1) in ovarian cancer development. However, dynamic crosstalk between BRCA1 and SIRT1 is poorly understood. Here, we showed that: (i) BRCA1 inactivation events (mutation, promoter methylation, or knockdown) were accompanied by decrease...

BACKGROUND Sirtuin (Sirt), a sensor of the cell metabolic state, regulates glucose and lipid metabolism. The aim of this study was to address whether rosiglitazone (RGZ) alters hepatic Sirt1 and whether Sirt1 and/or Sirt6 have a regulatory role in the protective effects of RGZ on hepatocyte steatosis. METHODS To investigate the effect of RGZ on hepatic Sirt1, rats were administered with RGZ f...

The exocrine pancreas can undergo acinar-to-ductal metaplasia (ADM), as in the case of pancreatitis where precursor lesions of pancreatic ductal adenocarcinoma (PDAC) can arise. The NAD(+)-dependent protein deacetylase Sirtuin-1 (Sirt1) has been implicated in carcinogenesis with dual roles depending on its subcellular localization. In this study, we examined the expression and the role of Sirt1...

Human Silent Information Regulator Type 1 (SIRT1) is an NAD(+)-dependent deacetylase protein which is an intermediary of cellular metabolism in gene silencing and aging. SIRT1 has been extensively investigated and shown to delay senescence; however, less is known about the regulation of SIRT1 during aging. In this study, we show that the peroxisome proliferator-activated receptor-γ (PPARγ), whi...

SIRT1 takes down tumors Y uan et al. have identifi ed another anti-cancer effect of the “longevity” protein SIRT1. By speeding the destruction of the tumor promoter c-Myc, SIRT1 curbs cell division. The yeast and nematode equivalents of SIRT1 are fountains of youth that stretch lifespan. Whether SIRT1 slows aging in mammals isn’t certain, but it’s benefi cial in other ways. The protein tunes up...