Linked Life Data

16958678

Source:http://linkedlifedata.com/resource/pubmed/id/16958678

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2006-9-8
pubmed:abstractText
Intragastric ethanol feeding in mice induces expression of unfolded protein response/endoplasmic reticulum (UPR/ER) stress response genes. The proximate cause appears to be hyperhomocysteinemia, a well-known cause of ER stress in other contexts. Hyperhomocysteinemia appears to be due to downregulation of methionine synthase. The importance of homocysteine and ER stress in the pathogenesis of liver disease was suggested by the prevention of the alcohol-induced changes by feeding sufficient betaine to lower homocysteine via betaine homocysteine methyl transferase. The ER stress, via CHOP, causes apoptosis and CHOP null mice exhibit no apoptosis. Alcohol-induced ER stress can activate sterol regulatory element-binding protein (SREBP)-1c and SREBP-2, which contribute to the accumulation of triglyceride and cholesterol. Hyperhomocysteinemia, ER stress and pathological changes of alcohol were minimally affected by absence of tumor necrosis factor receptor 1 (TNFR1) and the effect of betaine was also independent of TNF signaling. At present ER stress as an important factor in the pathogenesis of alcoholic liver disease is an exciting new hypothesis and ongoing research will need to further clarify its contribution. Among the issues in need of further elucidation are the role of ER stress induced by alcohol in SREBP regulation and fatty liver, as well as the precise mechanism of protection by betaine: decreased homocysteine, decreased S-adenosylhomocysteine, or increased S-adenosylmethionine.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0815-9319
pubmed:author
pubmed:issnType
Print
pubmed:volume
21 Suppl 3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S7-9
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Unfolding new mechanisms of alcoholic liver disease in the endoplasmic reticulum.
pubmed:affiliation
USC-UCLA Research Center for Alcoholic Liver, USC Research Center for Liver Disease, Division of Gastrointestinal, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. kaplowit@usc.edu
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural