Source:http://linkedlifedata.com/resource/pubmed/id/16391241
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rdf:type | |
lifeskim:mentions |
umls-concept:C0016030,
umls-concept:C0018787,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0034802,
umls-concept:C0040624,
umls-concept:C0079281,
umls-concept:C0079411,
umls-concept:C0085536,
umls-concept:C0086982,
umls-concept:C0162772,
umls-concept:C0205374,
umls-concept:C1314939,
umls-concept:C1334043,
umls-concept:C2697616
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pubmed:issue |
4
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pubmed:dateCreated |
2006-3-22
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pubmed:abstractText |
Endothelin-1 (ET-1) is implicated in fibroblast proliferation, which results in cardiac fibrosis. Both reactive oxygen species (ROS) generation and epidermal growth factor receptor (EGFR) transactivation play critical roles in ET-1 signal transduction. In this study, we used rat cardiac fibroblasts treated with ET-1 to investigate the connection between ROS generation and EGFR transactivation. ET-1 treatment was found to stimulate the phosphorylation of EGFR and ROS generation, which were abolished by ETA receptor antagonist N-(N-(N-((hexahydro-1H-azepin-1-yl)carbonyl)-L-leucyl)-D-tryptophyl)-D-tryptophan (BQ485). NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI), ROS scavenger N-acetyl cysteine (NAC), and p47phox small interfering RNA knockdown all inhibited the EGFR transactivation induced by ET-1. In contrast, EGFR inhibitor 4-(3'-chloroanilino)-6,7-dimethoxyquinazoline (AG-1478) cannot inhibit intracellular ROS generation induced by ET-1. Src homology 2-containing tyrosine phosphatase (SHP-2) was shown to be associated with EGFR during ET-1 treatment by EGFR coimmunoprecipitation. ROS have been reported to transiently oxidize the catalytic cysteine of phosphotyrosine phosphatases to inhibit their activity. We examined the effect of ROS on SHP-2 in cardiac fibroblasts using a modified malachite green phosphatase assay. SHP-2 was transiently oxidized during ET-1 treatment, and this transient oxidization could be repressed by DPI or NAC treatment. In SHP-2 knockdown cells, ET-1-induced phosphorylation of EGFR was dramatically elevated and is not influenced by NAC and DPI. However, this elevation was suppressed by GM6001 [a matrix metalloproteinase (MMP) inhibitor] and heparin binding (HB)-epidermal growth factor (EGF) neutralizing antibody. Our data suggest that ET-1-ETA-mediated ROS generation can transiently inhibit SHP-2 activity to facilitate the MMP-dependent and HB-EGF-stimulated EGFR transactivation and mitogenic signal transduction in rat cardiac fibroblasts.
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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/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0026-895X
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pubmed:author |
pubmed-author:ChenCheng-HsienCH,
pubmed-author:ChenJin-JerJJ,
pubmed-author:ChenYee-ShiuanYS,
pubmed-author:ChenYen-LingYL,
pubmed-author:ChengChing-FengCF,
pubmed-author:ChengTzu-HurngTH,
pubmed-author:ChiuWen-TaWT,
pubmed-author:LianWei-ShiungWS,
pubmed-author:LinHengH,
pubmed-author:MengTzu-ChingTC,
pubmed-author:ShihNeng-LangNL
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pubmed:issnType |
Print
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pubmed:volume |
69
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1347-55
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16391241-Animals,
pubmed-meshheading:16391241-Endothelin-1,
pubmed-meshheading:16391241-Immunoprecipitation,
pubmed-meshheading:16391241-Oxidation-Reduction,
pubmed-meshheading:16391241-Protein Tyrosine Phosphatases,
pubmed-meshheading:16391241-Rats,
pubmed-meshheading:16391241-Reactive Oxygen Species,
pubmed-meshheading:16391241-Receptor, Epidermal Growth Factor,
pubmed-meshheading:16391241-Signal Transduction,
pubmed-meshheading:16391241-Transcriptional Activation,
pubmed-meshheading:16391241-src Homology Domains
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pubmed:year |
2006
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pubmed:articleTitle |
Reactive oxygen species generation is involved in epidermal growth factor receptor transactivation through the transient oxidization of Src homology 2-containing tyrosine phosphatase in endothelin-1 signaling pathway in rat cardiac fibroblasts.
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pubmed:affiliation |
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China.
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pubmed:publicationType |
Journal Article
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