Navigation Links
Proteasome inhibition affects epigenetic mechanisms
Date:2/19/2009

Alcohol consumption causes alteration in several cellular mechanisms, and leads to inflammation, apoptosis, immunoresponse defect, and fibrosis. These phenomena are associated to significant changes in the epigenetic mechanisms, and, subsequently, to the liver cell memory. Although inhibition of proteasome function has been widely reported in models of alcoholic liver disease (ALD), why proteasome dysfunction may enhance hepatotoxicity is not well defined. In addition, there is no evidence of the effect of ethanol feeding on the activity of nuclear proteasome and the consequences of proteasome inhibition in epigenetic mechanisms and DNA repair.

A research team led by Dr. Fawzia Bardag-Gorce, from United States examined the effects of ethanol-induced proteasome inhibition, and the effects of proteasome inhibition in the regulation of epigenetic mechanisms.Their study will be published on February 14, 2009 in the World Journal of Gastroenterology.

In their study, rats were fed ethanol for one moth using the Tsukamoto-French model and were compared to rats given the proteasome inhibitor PS-341 (Bortezomib, Velcade) by intraperitoneal injection. Microarray analysis and Real time PCR were performed and proteasome activity assays and Western blot analysis were performed using isolated nuclei.

They found that 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 related to an increase in histone acetylation, and it is hypothesized that the proteasome proteolytic activity regulated histone modifications by controlling the stability of histone modifying enzymes, and, therefore, regulated the chromatin structure, allowing easy access to chromatin by RNA polymerase, and, thus, proper gene expression. Proteasome inhibition by PS-341 increased histone acetylation similar to chronic ethanol feeding. In addition, proteasome inhibition caused dramatic changes in hepatic remethylation reactions as there was a significant decrease in the enzymes responsible for the regeneration of S-adenosylmethionine (SAMe), and, in particular, a significant decrease in the betainehomocysteine methyltransferase (BHMT) enzyme.

In conclusion, proteasome inhibition plays a critical role in regulating the gene expression of key enzymes in the remethylation pathway, such as betainehomocysteine methyltransferase (BHMT), and links to liver injury in alcoholic iver disease.


'/>"/>

Contact: Lai-Fu Li
wjg@wjgnet.com
86-105-908-0039
World Journal of Gastroenterology
Source:Eurekalert

Related medicine news :

1. Webinar on June 25 to Focus on Opportunity for Treating Chronic Pain, Migraine and Muscle Spasticity Through Inhibition of Neurotransmitter Glutamate
2. An effective strategy for inhibition of cirrhosis
3. Family history of alcoholism affects response to drug used to treat heavy drinking
4. Genetic variation affects smoking cessation treatment
5. Age affects motivation for quitting smoking
6. Updated: National Infertility Awareness Week Nov. 4-10; Infertility Affects Significant Number of Couples
7. Competition Affects Your Perception of Your Paycheck
8. Fetal Exposure to Arsenic Affects Genes
9. Childhood sleep-disordered breathing disproportionately affects obese and African-Americans
10. Got sugar? Glucose affects our ability to resist temptation
11. Where vets served affects frequency of ER visits but not hospital stays
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/16/2017)... ... January 16, 2017 , ... Permobil has just completed ... of custom seating systems has a well-earned reputation for premium quality, with a ... innovation and growth in the custom seating business, which enjoys strong demand, and ...
(Date:1/16/2017)... CA (PRWEB) , ... January 16, 2017 , ... ... manuscript in the Aesthetic Surgery Journal , the official journal of The ... conducted on lower eyelid retraction surgery. The procedure is designed to correct drooping, ...
(Date:1/16/2017)... (PRWEB) , ... January 16, 2017 , ... NexTec Group ... a group of 100 organizations honored for their accomplishments in the field of midmarket ... growth, industry leadership and recognition, and innovation. Selection is not based on revenue and ...
(Date:1/15/2017)... ... January 15, 2017 , ... "On Tour is a music themed ... and ease," said Christina Austin - CEO of Pixel Film Studios. , On ... edit the style and animation of their slideshows. Place each slide on top of ...
(Date:1/14/2017)... ... 2017 , ... Healthy living brand Moody Zook recently came ... With more and more people opting to go organic in their lifestyle, the ... to specific needs. , Moody Zook focused particularly on their newly launched activated ...
Breaking Medicine News(10 mins):
(Date:1/13/2017)... 13, 2017  Alfalfa, cattle, leafy greens and rosy cheeked ... film , which emphasizes the food industry,s shift from response ... COPAN,s Swab Rinse Kit (SRK™) ... sampling process in the wake of the new FDA ... COPAN is expanding the U.S. production of the ...
(Date:1/13/2017)... 13, 2017 The 2016 election resulted ... several states voting in favor of legalizing cannabis for recreational ... market in the U.S. In addition, the state of ... annual cannabis products sales. The ArcView Group has published an ... legal cannabis sales in the U.S. last year reached $6.7 billion, ...
(Date:1/13/2017)... 2017 Research and Markets has announced the ... report to their offering. ... Cystic fibrosis (CF) is a progressive genetic condition ... fibroses transmembrane conductance regulator (CFTR) gene from both parents. The defective ... and result in the buildup of a thick and sticky mucus ...
Breaking Medicine Technology: