Taipei Medical University

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Che CH
------>authors3_c=
------>paper_class1=1
------>Impact_Factor=5.080
------>paper_class3=2
------>paper_class2=1
------>vol=69
------>confirm_bywho=shtsai
------>insert_bywho=wtchiu
------>Jurnal_Rank=8.6
------>authors4_c=
------>comm_author=
------>patent_EDate=None
------>authors5_c=
------>publish_day=1
------>paper_class2Letter=None
------>page2=1355
------>medlineContent=
------>unit=J0600
------>insert_date=20060501
------>iam=7
------>update_date=None
------>author=???
------>change_event=4
------>ISSN=
------>authors_c=
------>score=500
------>journal_name=MOLECULAR PHARMACOLOGY
------>paper_name=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
------>confirm_date=20060501
------>tch_id=073010
------>pmid=16391241
------>page1=1347
------>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=13517
------>authors2=Cheng TH
------>authors3=Lin H
------>authors4=Shih NL
------>authors5=Chen YL
------>authors6=Chen YS, Cheng CF,Lian WS,Meng TC,Chiu WT
------>authors6_c=
------>authors=Che CH
------>delete_flag=0
------>SCI_JNo=None
------>authors2_c=
------>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
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z