Linked Life Data

11007794

Source:http://linkedlifedata.com/resource/pubmed/id/11007794

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
2001-1-8
pubmed:abstractText
Hepatic stellate cells (HSC) undergo activation toward myofibroblast-like cells during early stages of liver injury associated with fibrogenesis. Platelet-derived growth factor (PDGF), particularly its BB isoform, has been identified as the most potent mitogen for HSC. 4-Hydroxy-2,3-nonenal and related 4-hydroxy-2, 3-alkenals (HAKs) have been suggested to modulate the process of HSC activation. In this study we investigated the relationship between HAKs and PDGF receptor activation in human HSC. By employing noncytotoxic concentrations (10(-6) m) of HAKs, we observed a significant inhibition of PDGF-BB-dependent DNA synthesis. HAKs inhibited relevant pathways of PDGF-BB-dependent mitogenic signaling, including autophosphorylation of PDGF receptor (PDGF-R) beta subunits and activation of phosphatidylinositol 3-kinase and extracellular regulated kinases 1/2. Inhibition of DNA synthesis was reversible, and recovery of PDGF-mediated mitogenic signaling occurred within 24-48 h and was associated with HAKs-induced up-regulation of PDGF-R beta gene expression. 4-Hydroxy-2,3-nonenal, used as a model HAK, inhibited the intrinsic tyrosine kinase activity associated with the PDGF-R beta subunit, whereas binding of PDGF to its receptor was unaffected. This study identifies a novel regulatory mechanism of reactive aldehydes on PDGF receptor signaling and biologic actions, which may be relevant in several pathophysiological conditions, including liver fibrosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
40561-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Interaction between 4-hydroxy-2,3-alkenals and the platelet-derived growth factor-beta receptor. Reduced tyrosine phosphorylation and downstream signaling in hepatic stellate cells.
pubmed:affiliation
Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, 10125 Torino, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't