Linked Life Data

9254052

Source:http://linkedlifedata.com/resource/pubmed/id/9254052

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1997-10-10
pubmed:abstractText
Previously, our laboratory has shown that oxidized low density lipoproteins (Ox-LDL) can exert a concentration-dependent stimulation in the proliferation of aortic smooth muscle cells, "a hallmark in the pathogenesis of atherosclerosis" (Chatterjee, S. (1992) Mol. Cell. Biochem., 111, 143-147). Here we report a novel aspect of Ox-LDL-mediated signal transduction. We demonstrate that in aortic smooth muscle cells, Ox-LDL stimulates the activity of a UDP-galactose:glucosylceramide beta1-->4 galactosyltransferase (GalT-2) and phosphorylation/activation of p44 mitogen-activated protein (MAP) kinase (p44 MAPK). The activity of GalT-2 increased about 2-fold within 2.5-5 min of incubation of cells with Ox-LDL (10 microg/ml). After 5 min of incubation of cells with Ox-LDL, but not LDL, there was a 2-fold increase in the activity of p44 MAPK. Phosphoamino acid analysis employing thin layer chromatography revealed that the tyrosine and threonine moieties of p44 MAPK was phosphorylated by Ox-LDL. D-1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP; a potent inhibitor of GalT-2) impaired the Ox-LDL mediated induction of p44 MAPK activity and the phosphorylation of tyrosine and threonine residues in p44 MAPK. This phenomenon was bypassed by the simultaneous addition of lactosylceramide. The upstream and downstream parameters in MAP kinase signaling pathways were investigated next. We found that Ox-LDL stimulated (9-fold) the loading of GTP on Ras. Interestingly, Ox-LDL specifically induced c-fos mRNA expression (6.5-fold) in these cells, as compared to the control. Thus, one of the biochemical mechanisms in Ox-LDL mediated induction in the proliferation in aortic smooth muscle cells may involve GalT-2 activation, lactosylceramide production, Ras GTP loading, activation of the kinase cascade, and c-fos expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0959-6658
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
703-10
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Oxidized low density lipoproteins stimulate galactosyltransferase activity, ras activation, p44 mitogen activated protein kinase and c-fos expression in aortic smooth muscle cells.
pubmed:affiliation
Department of Pediatrics, The Johns Hopkins University, School of Medicine, Baltimore, MD 21287-3654, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.