Source:http://linkedlifedata.com/resource/pubmed/id/17583675
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2007-7-3
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pubmed:abstractText |
Previous studies demonstrated an important interaction between nuclear factor-kappaB (NF-kappaB) activation and homocysteine (Hcy)-induced cytokines expression in endothelial cells and vascular smooth muscle cells. However, the underlying mechanism remains illusive. In this study, we investigated the effects of Hcy on NF-kappaB-mediated sICAM-1, TNF-alpha production and the possible involvement of ERK(1/2)/p38MAPK pathway. The effects of rosiglitazone intervention were also examined. Our results show that Hcy increased the levels of sICAM-1 and TNF-alpha in cultured human umbilical vein endothelial cells (HUVECs) in a time- and concentration-dependent manner. This effect was significantly depressed by rosiglitazone and different inhibitors (PDTC, NF-kappaB inhibitor; PD98059, MEK inhibitor; SB203580, p38MAPK specific inhibitor; and staurosporine, PKC inhibitor). Next, we investigated the effect of Hcy on ERK(1/2)/p38MAPK pathway and NF-kappaB activity in HUVECs. The results show that Hcy activated both ERK(1/2)/p38MAPK pathway and NF-kappaB-DNA-binding activity. These effects were markedly inhibited by rosiglitazone as well as other inhibitors (SB203580, PD98059, and PDTC). Further, the pretreatment of staurosporine abrogated ERK(1/2)/p38MAPK phosphorylation, suggesting that Hcy-induced ERK(1/2)/p38MAPK activation is associated with PKC activity. Our results provide evidence that Hcy-induced NF-kappaB activation was mediated by activation of ERK(1/2)/p38MAPK pathway involving PKC activity. Rosiglitazone reduces the NF-kappaB-mediated sICAM-1 and TNF-alpha production induced by Hcy via inhibition of ERK(1/2)/p38MAPK pathway.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/rosiglitazone
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-291X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
360
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17583675-Cells, Cultured,
pubmed-meshheading:17583675-Dose-Response Relationship, Drug,
pubmed-meshheading:17583675-Endothelial Cells,
pubmed-meshheading:17583675-Enzyme Activation,
pubmed-meshheading:17583675-Humans,
pubmed-meshheading:17583675-Intercellular Adhesion Molecule-1,
pubmed-meshheading:17583675-MAP Kinase Signaling System,
pubmed-meshheading:17583675-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:17583675-NF-kappa B,
pubmed-meshheading:17583675-Thiazolidinediones,
pubmed-meshheading:17583675-Tumor Necrosis Factor-alpha,
pubmed-meshheading:17583675-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2007
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pubmed:articleTitle |
Rosiglitazone attenuates NF-kappaB-dependent ICAM-1 and TNF-alpha production caused by homocysteine via inhibiting ERK1/2/p38MAPK activation.
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pubmed:affiliation |
Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.
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pubmed:publicationType |
Journal Article
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