Protein acetylation in sepsis - modulation by inhibitors of protein deacetylases (HDACi)
Acronym: Sephi
Principal Investigator: Katrin Noack
Scientific Advisors: Prof. Dr. T. Heinzel, PD Dr. O.H. Krämer
Research Ares: D Sepsis related Organ Failure
Project Number: D1.13
Duration: 05.10.2011 - 04.10.2014
Module: PhD Fellowship
The Problem
Animal experiments showed that histondeacetylase inhibitors (HDACi) have a positive effect of the sepsis outcome and survival of mice. The project aims to investigate molecular mechanisms and possible targets of the HDACi as well as identifying the involved HDACs.
Results so far
We analyzed the influence of HDACi on IL6 secretion after stimulation of mouse embryonic fibroblasts (MEF) with (WT) and without p53. ELISA-Tests showed that IL6 was secreted by both cell lines after LPS stimulation, while WT MEFs secreted more IL6 than MEFs lacking p53, indicating a role of p53 in IL6 secretion. After treatment with VPA, IL6 levels after short time incubation with LPS in WT-MEF-cells were very slightly increased, but after long time exposure to LPS there was almost no difference between the cells with and without VPA detectable. Further Western Blot analysis showed that NFκB was activated through LPS: after short time stimulation activating phosphorylation of NFκB could be detected. Still, activation of NFκB does not lead to transcriptional activation of NFκB-target genes associated with apoptosis. Therefore other NFκB-target genes might be responsible for the IL6 secretion.
Contact
Tel.: +49 (0)3641 - 9 49 354
Friedrich-Schiller-Universität Jena
Institut für Biochemie und Biophysik, CMB
Hans-Knöll-Straße 2
07745 Jena