%0 Journal Article
%T E. coli Endotoxin Modulates the Expression of Sirtuin Proteins in PBMC in Humans
%A Angela Storka
%A Gerhard F邦hrlinger
%A Martin Seper
%A Lisa Wang
%A Michael Jew
%A Asha Leisser
%A Michael Wolzt
%J Mediators of Inflammation
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/876943
%X Background. Sirtuin (SIRT) proteins are class I histone deacetylases displaying gene regulatory functions in inflammatory, cancer, and metabolic diseases. These SIRT actions involve the nuclear factor 百B and its inhibitor I百B pathway. However, the regulation of SIRT in vivo is still unclear. Material and Methods. In a human endotoxemia model, 20 healthy male subjects received an intravenous bolus of 2ˋng/kg body weight Escherichia coli endotoxin (LPS). SIRT expression was investigated in peripheral blood mononuclear cells (PBMC) with qPCR and Western blot before and 3 hours, 6 hours, and 24 hours after LPS challenge. Additionally, SIRT regulation was studied in vitro in cultivated PBMC after incubation with 20ˋng/mL LPS. Results. A downregulation by >40% of SIRT1 mRNA was detectable 3 hours after LPS and of SIRT3 mRNA 6 hours after LPS. SIRT3, I百B汐, and I百B-汕 protein expressions were decreased 3 and 6 hours after LPS. SIRT2 mRNA or protein expression did not change following LPS. These findings were consistent in vitro and associated with augmented phosphorylation of I百B-汕. Discussion. In this E. coli endotoxemia model, SIRT1 and SIRT3 mRNA expressions in PBMC in humans were reduced after LPS challenge. This suggests that SIRT may represent an inflammatory target protein in vivo. 1. Background Nicotinamide phosphoribosyltransferase (Nampt), also known as pre-B-cell colony-enhancing factor 1 (PBEF1) or visfatin, is an enzyme in humans that catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, which is required in the biosynthesis of nicotinamide adenine dinucleotide ( ). As a pivotal component of an salvage pathway, Nampt is also a regulator of the activity of -dependent enzymes, such as class III histone/protein deacetylases (HDAC). Within this group are Sirtuin proteins, of which seven isoforms (SIRT1每7) have so far been identified in humans. Sirtuins possess a wide range of regulatory functions and are implicated in inflammatory diseases, cancer, and aging [1]. The founding Sirtuin member, SIRT1, is associated with stress resistance, metabolism, apoptosis, senescence, differentiation, and aging [1] by directly regulating gene expression through its epigenetic activity on histones and gene silencing [2]. SIRT2, a tubulin deacetylase, functions as a mitotic checkpoint protein [3] and mediates mitotic cell death in response to DNA damage [4]. Recently, it has also been shown that SIRT1 and SIRT2 exert anti-inflammatory effects by deacetylating the RelA/p65 subunit of nuclear factor 百B
%U http://www.hindawi.com/journals/mi/2013/876943/