Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-3
pubmed:abstractText
Platelet-derived growth factor-B (PDGF-B) is upregulated by proinflamatory stimuli in the early stages of atherosclerosis. However, its mechanisms are not fully elucidated. In the present study, by using the antioxidant N-acetylcysteine (NAC), we investigated in human umbilical vein endothelial cells (HUVECs) the roles of oxidative stress in PDGF-B expression induced by tumor necrosis factor alpha (TNFalpha) and its underlying mechanisms. Exposure of HUVECs to TNFalpha (200 U/ml) for 24 hours caused significant increases of both the PDGF-B expression and its promoter/enhancer activity, which were abolished by NAC (20 mmol/L). Accordingly, a prolonged oxidative stress was induced by TNFalpha and that was prevented by pretreatment with NAC. Electrophoresis mobility shift assay (EMSA) and Western blot analysis showed that both the nuclear factor-kappaB (NF-kappaB) and the specificity protein-1 (SP-1) were activated by TNFalpha. However, NAC only partially inhibited the TNFalpha-induced activation of NF-kappaB, but abolished the activation of SP-1. Mutation of the NF-kappaB binding site resulted in a moderate reduction in the TNFalpha-induced activity of PDGF-B promoter/enhancer, whereas mutation of SP-1 binding site resulted in an absence of induction by TNFalpha. These results suggest that oxidative stress mediates the TNFalpha-induced expression of PDGF-B in HUVECs through redox-sensitive transcription factors, predominantly the SP-1 and possibly, to some extent of NF-kappaB.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0160-2446
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26-34
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Roles of NF-kappaB and SP-1 in oxidative stress-mediated induction of platelet-derived growth factor-B by TNFalpha in human endothelial cells.
pubmed:affiliation
Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't