Cheng CM, Hong HJ, Liu JC, Shih NL, Juan SH, Loh SH, Chan P, Chen JJ, Cheng TH |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=63 ------>confirm_bywho=tlc ------>insert_bywho=thcheng ------>Jurnal_Rank=None ------>authors4_c=None ------>comm_author=1 ------>patent_EDate=None ------>authors5_c=None ------>publish_day=None ------>paper_class2Letter=None ------>page2=1011 ------>medlineContent= ------>unit=E0109 ------>insert_date=20030522 ------>iam=7 ------>update_date= ------>author=??? ------>change_event=5 ------>ISSN=None ------>authors_c=None ------>score=500 ------>journal_name=Mol Pharmacol ------>paper_name=Crucial role of extracellular signal-regulated kinase pathway in reactive oxygen species-mediated endothelin-1 gene expression induced by endothelin-1 in rat cardiac fibroblasts. ------>confirm_date=20031018 ------>tch_id=092006 ------>pmid=12695528 ------>page1=1002 ------>fullAbstract=Endothelin-1 (ET-1) has been implicated in fibroblast proliferation. However, the mechanism involving ET-1 is not clear. The present study was performed to examine the role of endogenous ET-1 in ET-1-stimulated fibroblast proliferation and to investigate the regulatory mechanism of ET-1-induced ET-1 gene expression in cardiac fibroblasts. Both ET(A) receptor antagonist [(hexahydro-1H-azepinyl)carbonyl-Leu-D-Trp-D-OH (BQ485)] and endothelin-converting enzyme inhibitor (phosphoramidon) inhibited the increased DNA synthesis caused by ET-1. ET-1 gene was induced by ET-1, as revealed with Northern blotting and ET-1 promoter activity assay. ET-1 increased intracellular reactive oxygen species (ROS), which were significantly inhibited by BQ485 and antioxidants. Antioxidants suppressed ET-1 gene expression and DNA synthesis stimulated by ET-1. ET-1 activated mitogen-activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase, which were significantly inhibited by antioxidants. Only ERK inhibitor U0126 could inhibit ET-1-induced transcription of the ET-1 gene. Cotransfection of dominant-negative mutant of Ras, Raf, and MEK1 decreased the ET-1-induced increase in ET-1 transcription, suggesting that the Ras-Raf-ERK pathway is required for ET-1 action. Truncation and mutational analysis of the ET-1 gene promoter showed that the activator protein-1 (AP-1) binding site was an important cis-element in ET-1-induced ET-1 gene expression. Antioxidants attenuated the ET-1-stimulated AP-1 binding activity. Our data suggest that ROS were involved in ET-1-induced fibroblast proliferation and mediated ET-1-induced activation of ERK pathways, which culminated in ET-1 gene expression. ------>tmu_sno=None ------>sno=7335 ------>authors2=None ------>authors3=None ------>authors4=None ------>authors5=None ------>authors6=None ------>authors6_c=None ------>authors=Cheng CM, Hong HJ, Liu JC, Shih NL, Juan SH, Loh SH, Chan P, Chen JJ, Cheng TH ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=Crucial role of extracellular signal-regulated kinase pathway in reactive oxygen species-mediated endothelin-1 gene expression induced by endothelin-1 in rat cardiac fibroblasts. ------>language=2 ------>check_flag= ------>submit_date= ------>country=None ------>no=5 ------>patent_SDate=None ------>update_bywho= ------>publish_year=2003 ------>submit_flag= ------>publish_month=None |