pubmed-article:16391241 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0034721 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0034693 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0034802 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0079281 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0018787 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0016030 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0085536 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0162772 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0040624 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0086982 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0079411 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C0205374 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C1334043 | lld:lifeskim |
pubmed-article:16391241 | lifeskim:mentions | umls-concept:C2697616 | lld:lifeskim |
pubmed-article:16391241 | pubmed:issue | 4 | lld:pubmed |
pubmed-article:16391241 | pubmed:dateCreated | 2006-3-22 | lld:pubmed |
pubmed-article:16391241 | 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. | lld:pubmed |
pubmed-article:16391241 | pubmed:language | eng | lld:pubmed |
pubmed-article:16391241 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16391241 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:16391241 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16391241 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16391241 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16391241 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16391241 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:16391241 | pubmed:month | Apr | lld:pubmed |
pubmed-article:16391241 | pubmed:issn | 0026-895X | lld:pubmed |
pubmed-article:16391241 | pubmed:author | pubmed-author:ChengChing-Fe... | lld:pubmed |
pubmed-article:16391241 | pubmed:author | pubmed-author:MengTzu-Ching... | lld:pubmed |
pubmed-article:16391241 | pubmed:author | pubmed-author:ChiuWen-TaWT | lld:pubmed |
pubmed-article:16391241 | pubmed:author | pubmed-author:ChenYen-LingY... | lld:pubmed |
pubmed-article:16391241 | pubmed:author | pubmed-author:LinHengH | lld:pubmed |
pubmed-article:16391241 | pubmed:author | pubmed-author:ChengTzu-Hurn... | lld:pubmed |
pubmed-article:16391241 | pubmed:author | pubmed-author:ChenJin-JerJJ | lld:pubmed |
pubmed-article:16391241 | pubmed:author | pubmed-author:ChenCheng-Hsi... | lld:pubmed |
pubmed-article:16391241 | pubmed:author | pubmed-author:ShihNeng-Lang... | lld:pubmed |
pubmed-article:16391241 | pubmed:author | pubmed-author:ChenYee-Shiua... | lld:pubmed |
pubmed-article:16391241 | pubmed:author | pubmed-author:LianWei-Shiun... | lld:pubmed |
pubmed-article:16391241 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:16391241 | pubmed:volume | 69 | lld:pubmed |
pubmed-article:16391241 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:16391241 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:16391241 | pubmed:pagination | 1347-55 | lld:pubmed |
pubmed-article:16391241 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
pubmed-article:16391241 | pubmed:meshHeading | pubmed-meshheading:16391241... | lld:pubmed |
pubmed-article:16391241 | pubmed:meshHeading | pubmed-meshheading:16391241... | lld:pubmed |
pubmed-article:16391241 | pubmed:meshHeading | pubmed-meshheading:16391241... | lld:pubmed |
pubmed-article:16391241 | pubmed:meshHeading | pubmed-meshheading:16391241... | lld:pubmed |
pubmed-article:16391241 | pubmed:meshHeading | pubmed-meshheading:16391241... | lld:pubmed |
pubmed-article:16391241 | pubmed:meshHeading | pubmed-meshheading:16391241... | lld:pubmed |
pubmed-article:16391241 | pubmed:meshHeading | pubmed-meshheading:16391241... | lld:pubmed |
pubmed-article:16391241 | pubmed:meshHeading | pubmed-meshheading:16391241... | lld:pubmed |
pubmed-article:16391241 | pubmed:meshHeading | pubmed-meshheading:16391241... | lld:pubmed |
pubmed-article:16391241 | pubmed:meshHeading | pubmed-meshheading:16391241... | lld:pubmed |
pubmed-article:16391241 | pubmed:meshHeading | pubmed-meshheading:16391241... | lld:pubmed |
pubmed-article:16391241 | pubmed:year | 2006 | lld:pubmed |
pubmed-article:16391241 | 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. | lld:pubmed |
pubmed-article:16391241 | pubmed:affiliation | Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China. | lld:pubmed |
pubmed-article:16391241 | pubmed:publicationType | Journal Article | lld:pubmed |
http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16391241 | lld:pubmed |
http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16391241 | lld:pubmed |
http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16391241 | lld:pubmed |
http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16391241 | lld:pubmed |
http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16391241 | lld:pubmed |
http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16391241 | lld:pubmed |
http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16391241 | lld:pubmed |
http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16391241 | lld:pubmed |