Uric acid stimulates |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=1.676 ------>paper_class3=2 ------>paper_class2=1 ------>vol=29 ------>confirm_bywho=ncchang ------>insert_bywho=hippy ------>Jurnal_Rank=36.8 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=1312 ------>medlineContent= ------>unit=E0100 ------>insert_date=20091015 ------>iam=4 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=Acta Pharmacol Sin. ------>paper_name=Uric acid stimulates endothelin-1 gene expression associated with NADPH oxidase in human aortic smooth muscle cells. ------>confirm_date=20091016 ------>tch_id=093148 ------>pmid=18954524 ------>page1=1301 ------>fullAbstract=AIM: Recent experimental and human studies have shown that hyperuricemia is associated with hypertension and cardiovascular diseases. Elevated levels of endothelin-1 (ET-1) has been regarded as one of the most powerful independent predictors of cardiovascular diseases. For investigating whether uric acidinduced vascular diseases are related to ET-1, the uric acid-induced ET-1 expression in human aortic smooth muscle cells (HASMC) was examined. METHODS: Cultured HASMC treated with uric acid, cell proliferation and ET-1 expression were examined. Antioxidant pretreatments on uric acid-induced extracellular signal-regulated kinases (ERK) phosphorylation were carried out to elucidate the redox-sensitive pathway in proliferation and ET-1 gene expression. RESULTS: Uric acid was found to increase HASMC proliferation, ET-1 expression and reactive oxygen species production. The ability of both N-acetylcysteine and apocynin (1-[4-hydroxy-3-methoxyphenyl]ethanone, a NADPH oxidase inhibitor) to inhibit uric acid-induced ET-1 secretion and cell proliferation suggested the involvement of intracellular redox pathways. Furthermore, apocynin, and p47phox small interfering RNA knockdown inhibited ET-1 secretion and cell proliferation induced by uric acid. Inhibition of ERK by U0126 (1,4-diamino-2,3-dicyano- 1,4-bis[2-aminophenylthio]butadiene) significantly suppressed uric acid-induced ET-1 expression, implicating this pathway in the response to uric acid. In addition, uric acid increased the transcription factor activator protein-1 (AP-1) mediated reporter activity, as well as the ERK phosphorylation. Mutational analysis of the ET-1 gene promoter showed that the AP-1 binding site was an important cis-element in uric acid-induced ET-1 gene expression. CONCLUSION: This is the first observation of ET-1 regulation by uric acid in HASMC, which implicates the important role of uric acid in the vascular changes associated with hypertension and vascular diseases. ------>tmu_sno=None ------>sno=22702 ------>authors2=Liu JC ------>authors3=Lin JW ------>authors4=Chen CH ------>authors5=Wu CH ------>authors6=Cheng TH ------>authors6_c= ------>authors=Uric acid stimulates ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Uric acid stimulates endothelin-1 gene expression associated with NADPH oxidase in human aortic smooth muscle cells. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=11 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2008 ------>submit_flag=None ------>publish_month=11 |