Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-10-22
pubmed:abstractText
Elevated plasma levels of homocysteine have been shown to interfere with normal cell function in a variety of tissues and organs, such as the vascular wall and the liver. However, the molecular mechanisms behind homocysteine effects are not completely understood. In order to better characterize the cellular effects of homocysteine, we have searched for changes in gene expression induced by this amino acid. Our results show that homocysteine is able to induce the expression and synthesis of the tissue inhibitor of metalloproteinases-1 (TIMP-1) in a variety of cell types ranging from vascular smooth muscle cells to hepatocytes, HepG2 cells and hepatic stellate cells. In this latter cell type, homocysteine also stimulated alpha 1(I) procollagen mRNA expression. TIMP-1 induction by homocysteine appears to be mediated by its thiol group. Additionally, we demonstrate that homocysteine is able to promote activating protein-1 (AP-1) binding activity, which has been shown to be critical for TIMP-1 induction. Our findings suggest that homocysteine may alter extracellular matrix homeostasis on diverse tissular backgrounds besides the vascular wall. The liver could be considered as another target for such action of homocysteine. Consequently, the elevated plasma levels of this amino acid found in different pathological or nutritional circumstances may cooperate with other agents, such as ethanol, in the onset of liver fibrosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
1455
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12-22
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10524225-Animals, pubmed-meshheading:10524225-Blotting, Northern, pubmed-meshheading:10524225-Cells, Cultured, pubmed-meshheading:10524225-Cysteine, pubmed-meshheading:10524225-DNA, Complementary, pubmed-meshheading:10524225-Dose-Response Relationship, Drug, pubmed-meshheading:10524225-Extracellular Matrix, pubmed-meshheading:10524225-Gene Expression Regulation, pubmed-meshheading:10524225-Homocysteine, pubmed-meshheading:10524225-Liver, pubmed-meshheading:10524225-Liver Cirrhosis, Experimental, pubmed-meshheading:10524225-Mercaptoethanol, pubmed-meshheading:10524225-Muscle, Smooth, Vascular, pubmed-meshheading:10524225-Polymerase Chain Reaction, pubmed-meshheading:10524225-Procollagen, pubmed-meshheading:10524225-RNA, Messenger, pubmed-meshheading:10524225-Rats, pubmed-meshheading:10524225-Tissue Inhibitor of Metalloproteinase-1, pubmed-meshheading:10524225-Transcription Factor AP-1
pubmed:year
1999
pubmed:articleTitle
Induction of TIMP-1 expression in rat hepatic stellate cells and hepatocytes: a new role for homocysteine in liver fibrosis.
pubmed:affiliation
Department of Medicine, School of Medicine, Universidad de Navarra, Pamplona, Spain.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't