| Hong HJ, Chan P |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=61 ------>confirm_bywho=wslee ------>insert_bywho=juansh ------>Jurnal_Rank=None ------>authors4_c=None ------>comm_author= ------>patent_EDate=None ------>authors5_c=None ------>publish_day=None ------>paper_class2Letter=None ------>page2=68 ------>medlineContent= ------>unit=E0105 ------>insert_date=20040429 ------>iam=4 ------>update_date=None ------>author=??? ------>change_event=5 ------>ISSN=None ------>authors_c=None ------>score=500 ------>journal_name=Cardiovasc Res. 2004 Jan 1;61(1):159-68. ------>paper_name=Angiotensin II induces endothelin-1 gene expression via extracellular signal-regulated kinase pathway in rat aortic smooth muscle cells. ------>confirm_date=20040503 ------>tch_id=090103 ------>pmid=14732213 ------>page1=159 ------>fullAbstract=OBJECTIVE: Angiotensin II (Ang II) increases vascular endothelin-1 (ET-1) tissue levels, which in turn mediate a major part of Ang II-stimulated vascular growth and hypertension in vivo. Ang II also stimulates reactive oxygen species (ROS) generation in vascular smooth muscle cells (SMCs). However, whether ROS are involved in Ang II-induced ET-1 gene expression and the related intracellular mechanisms in vascular SMCs remains to be determined. METHODS: Cultured rat aortic SMCs were stimulated with Ang II, [3H]thymidine incorporation and the ET-1 gene expression was examined. Antioxidants pretreatment on Ang II-induced extracellular signal-regulated kinase (ERK) phosphorylation were performed to elucidate the redox-sensitive pathway in proliferation and ET-1 gene expression. RESULTS: Ang II-increased DNA synthesis was inhibited by AT(1) receptor antagonist (olmesartan) and ET(A) receptor antagonist (BQ485). ET-1 gene was induced with Ang II as revealed by Northern blotting and promoter activity assay. Ang II-increased intracellular ROS levels were inhibited by olmesartan and antioxidants. Antioxidants suppressed Ang II-induced ET-1 gene expression and ERK phosphorylation. An ERK inhibitor U0126 fully inhibited Ang II-induced ET-1 expression. Co-transfection of dominant negative mutant of Ras, Raf and MEK1 attenuated the Ang II-increased ET-1 promoter activity, suggesting that the Ras-Raf-ERK pathway is required for Ang II-induced ET-1 gene. Truncation and mutational analysis of the ET-1 gene promoter showed that activator protein-1 (AP-1) binding site was an important cis-element in Ang II-induced ET-1 gene expression. Moreover, Ang II- or H(2)O(2)-induced AP-1 reporter activities were also inhibited by antioxidants. CONCLUSIONS: Our data suggest that ROS are involved in Ang II-induced proliferation and the redox-sensitive ERK pathway plays a role in ET-1 gene expression in rat aortic SMCs. ------>tmu_sno=None ------>sno=8894 ------>authors2=Chan P ------>authors3=Liu JC ------>authors4=Juan SH ------>authors5=Huang MT ------>authors6=Lin JG, Cheng TH. ------>authors6_c=None ------>authors=Hong HJ, Chan P ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=Angiotensin II induces endothelin-1 gene expression via extracellular signal-regulated kinase pathway in rat aortic smooth muscle cells. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=1 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2004 ------>submit_flag=None ------>publish_month=None |