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:10/13/2017)... ... October 13, 2017 , ... While it’s often important to ... Fortunately, an inventor from Austin, Texas, has identified a solution. , She developed a ... or restricted lighting. As such, it eliminates the need to turn on a light ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... PurhealthRX ... CBD Oil utilizing Purzorb™ technology. Applying the Purzorb™process to full spectrum CBD oil will ... and providing a CBD form that can be easily incorporated into liquid products, while ...
(Date:10/13/2017)... ... 2017 , ... Apple Rehab Shelton Lakes , which specializes in the ... facility as part of a disaster drill on October 3rd. , Apple Rehab participated ... Emergency Manager, as well as the Connecticut Long Term Care Mutual Aid Plan ...
(Date:10/13/2017)... NY (PRWEB) , ... October 13, 2017 , ... Ellevate ... people in business to advocate for action towards gender equality at their inaugural Summit ... from around the globe, and reached a social audience of over 3 million. To ...
(Date:10/13/2017)... , ... October 13, 2017 , ... ... be giving viewers the lowdown on sciatica in a new episode of "Success ... focuses on current events and innovation and investigates each subject in-depth with passion ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... Cohen Veterans Bioscience and Early Signal Foundation announce a ... sensors for real-time monitoring of patients with trauma-related and ... focused on disruptive health solutions for rare disorders and ... record and integrate behavioral, cognitive, physiological and contextual data. ... ...
(Date:9/23/2017)... 22, 2017 Janssen Biotech, Inc. (Janssen) announced ... from the U.S. Food and Drug Administration (FDA) for ... for the treatment of moderately to severely active rheumatoid ... data are needed to further evaluate the safety of ... RA. "We ...
(Date:9/18/2017)... Mich. , Sept. 18, 2017  PMD Healthcare ... Specialty Pharmacy of Kalamazoo, Mich. , ... hub service that expedites and streamlines patient and provider ... PD 2.0, and wellness management services.  ... device used to measure lung function for a variety ...
Breaking Medicine Technology: