Epigenetics of proteasome inhibition in the liver of rats fed ethanol chronically.

ABSTRACT:

Aim

To examine the effects of ethanol-induced proteasome inhibition, and the effects of proteasome inhibition in the regulation of epigenetic mechanisms.

Methods

Rats were fed ethanol for 1 mo using the Tsukamoto-French model and were compared to rats given the proteasome inhibitor PS-341 (Bortezomib, Velcade(TM)) by intraperitoneal injection. Microarray analysis and real time PCR were performed and proteasome activity assays and Western blot analysis were performed using isolated nuclei.

Results

Chronic ethanol feeding caused a significant inhibition of the ubiquitin proteasome pathway in the nucleus, which led to changes in the turnover of transcriptional factors, histone-modifying enzymes, and, therefore, affected epigenetic mechanisms. Chronic ethanol feeding was

SUBMITTER: Oliva J 

PROVIDER: S-EPMC2653439 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature