Liu JC |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=4.711 ------>paper_class3=2 ------>paper_class2=1 ------>vol= ------>confirm_bywho=None ------>insert_bywho=hippy ------>Jurnal_Rank=10.2 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2= ------>medlineContent= ------>unit=E0100 ------>insert_date=20091015 ------>iam=2 ------>update_date=None ------>author=??? ------>change_event=1 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=Mol Pharmacol ------>paper_name=Urotensin II induces rat cardiomyocyte hypertrophy via the transient oxidization of Src homology 2-containing tyrosine phosphatase and transactivation of epidermal growth factor receptor. ------>confirm_date=None ------>tch_id=093148 ------>pmid=19755521 ------>page1= ------>fullAbstract=Urotensin II (U-II) is implicated in cardiomyocyte hypertrophy, which results in cardiac remodeling. We recently demonstrated that both reactive oxygen species (ROS) generation and epidermal growth factor receptor (EGFR) transactivation play critical roles in U-II signal transduction. However, the detailed intracellular mechanism(s) underlying cardiac hypertrophy and remodeling remain unclear. In this study, we used rat cardiomyocytes treated with U-II to investigate the association between ROS generation and EGFR transactivation. U-II treatment was found to stimulate cardiomyocyte hypertrophy through phosphorylation of EGFR and ROS generation. Apocynin, an NAD(P)H oxidase inhibitor, and the ROS scavenger N-acetyl cysteine (NAC), both inhibited EGFR transactivation induced by U-II. In contrast, AG-1478 (an EGFR inhibitor) failed to inhibit intracellular ROS generation induced by U-II. Src homology 2-containing tyrosine phosphatase (SHP-2), but not protein tyrosine phosphatase 1B (PTP 1B), was shown to be associated with EGFR during U-II treatment by EGFR co-immunoprecipitation. ROS have been reported to transiently oxidize the catalytic cysteine of phosphotyrosine phosphatases, subsequently inhibiting their activity. We examined the effect of U-II on SHP-2 and PTP 1B in cardiomyocytes using a modified malachite green phosphatase assay. SHP-2, but not PTP 1B, was transiently oxidized during U-II treatment, which could be repressed by NAC treatment. In SHP-2 knockdown cells, U-II-induced phosphorylation of EGFR and myocyte hypertrophy were dramatically elevated, and these effects were not influenced by NAC. Our data suggest that U-II-mediated ROS generation can transiently inhibit SHP-2 activity, thereby facilitating EGFR transactivation and hypertrophic signal transduction in rat cardiomyocytes. ------>tmu_sno=None ------>sno=22710 ------>authors2=Chen CH ------>authors3=Chen JJ ------>authors4=Cheng TH ------>authors5= ------>authors6= ------>authors6_c= ------>authors=Liu JC ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Urotensin II induces rat cardiomyocyte hypertrophy via the transient oxidization of Src homology 2-containing tyrosine phosphatase and transactivation of epidermal growth factor receptor. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2009 ------>submit_flag=None ------>publish_month=9 |