Linked Life Data

12529372

Source:http://linkedlifedata.com/resource/pubmed/id/12529372

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2003-4-21
pubmed:abstractText
Laminin is a basement-membrane protein that increases in liver fibrosis. To study the role of oxidative stress on laminin expression, hepatic stellate cells (HSC) were co-cultured with HepG2 cells that do or do not express (E47 or C34 cells, respectively) CYP2E1, a potent generator of oxygen radicals. Co-incubation of HSC with E47 cells increased laminin beta1 and gamma1 proteins compared with co-incubation with C34 cells; this increase was prevented by antioxidants and CYP2E1 inhibitors. Similar results were observed in co-culture with primary hepatocytes from saline- or pyrazole-treated (with high levels of CYP2E1) rats. Laminin alpha1 chain was not detectable in the HSC in any of the systems; however, laminin alpha2 chain increased in HSC co-cultured with E47 cells. Synthesis but not turnover of laminin beta1 and gamma1 proteins was increased in HSC in the E47 co-culture. Laminin beta1 and gamma1 mRNAs were up-regulated in HSC in the E47 co-culture because of transcriptional activation of both genes. Transfection experiments in HSC with reporter constructs driven by the laminin gamma1 promoter showed maximal responsiveness with the -230/+106 and the -1400/+106 constructs in the E47 system. Gel-shift assays demonstrated an increase in Sp1 binding to the laminin gamma1 promoter in HSC when co-incubated with E47 cells, which was blocked by an anti-Sp1 antibody. Co-transfection of a Sp1 expression vector further increased the responsiveness of the -330LAMgamma1-CAT reporter vector in HSC in the HSC/E47 system. These results show that diffusable CYP2E1-derived oxidative-stress mediators induce synthesis of laminins by a transcriptional mechanism in HSC. Such interactions between hepatocytes and HSC may be important during liver fibrosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15360-72
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Increased Sp1-dependent transactivation of the LAMgamma 1 promoter in hepatic stellate cells co-cultured with HepG2 cells overexpressing cytochrome P450 2E1.
pubmed:affiliation
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA. ny2000@hotmail.com
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't