| Chen CH |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=5.080 ------>paper_class3=2 ------>paper_class2=1 ------>vol= ------>confirm_bywho=ncchang ------>insert_bywho=hippy ------>Jurnal_Rank=8.6 ------>authors4_c=None ------>comm_author= ------>patent_EDate=None ------>authors5_c=None ------>publish_day=3 ------>paper_class2Letter=None ------>page2= ------>medlineContent= ------>unit=E0100 ------>insert_date=20060214 ------>iam=1 ------>update_date=None ------>author=??? ------>change_event=6 ------>ISSN= ------>authors_c=None ------>score=410 ------>journal_name=Molecular Pharmacology ------>paper_name=Reactive Oxygen Species Generation Is Involved in Epidermal Growth Factor Receptor Transactivation through The Transient Oxidization of SHP-2 in Endothelin-1 Signaling Pathway in Rat Cardiac Fibroblasts. ------>confirm_date=20081128 ------>tch_id=093148 ------>pmid=16391241 ------>page1= ------>fullAbstract=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-try ptophan (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. ------>tmu_sno=None ------>sno=12877 ------>authors2=Cheng TH ------>authors3=Lin H ------>authors4=Shih NL ------>authors5=Chen YL ------>authors6=Chen YS,Cheng CF,Lian WS,Meng TC,Chiu WT,Chen JJ ------>authors6_c=None ------>authors=Chen CH ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=0 ------>updateTitle=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. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2006 ------>submit_flag=None ------>publish_month=1 |