Chang MS |
------>authors3_c=??? ------>paper_class1=1 ------>Impact_Factor=2.355 ------>paper_class3=2 ------>paper_class2=1 ------>vol=60 ------>confirm_bywho=chshih43 ------>insert_bywho=bcchen ------>Jurnal_Rank=42.4 ------>authors4_c=??? ------>comm_author= ------>patent_EDate=None ------>authors5_c=??? ------>publish_day=1 ------>paper_class2Letter=None ------>page2=253 ------>medlineContent= ------>unit=E0400 ------>insert_date=20090325 ------>iam=2 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c=??? ------>score=500 ------>journal_name=Pharmacological Research ------>paper_name=Involvement of Ras/Raf-1/p44/42 MAPK in YC-1-induced cyclooxygenase-2 expression in human pulmonary epithelial cells ------>confirm_date=20091013 ------>tch_id=091057 ------>pmid=19717011 ------>page1=247 ------>fullAbstract=Our previous study demonstrated that 3-(5~-hydroxymethyl-2~-furyl)-1-benzylindazole (YC-1) might activate the soluble guanylate cyclase (sGC)/cGMP/protein kinase G (PKG) pathway to induce cyclooxygenase-2 (COX-2) expression in human pulmonary epithelial cells (A549). In this study, we further investigated the role of Raf-1 in YC-1-induced nuclear factor-kappaB (NF-kappaB) activation and COX-2 expression in A549 cells. YC-1-induced COX-2 expression was attenuated by a Raf-1 inhibitor (GW 5074) in a concentration-dependent manner. Treatment of A549 cells with YC-1 or 8-bromo-cGMP, a cell-permeable cGMP analogue, induced Raf-1 Ser338 phosphorylation in a time-dependent manner. YC-1-mediated Raf-1 activation was inhibited by an sGC inhibitor (ODQ), a PKG inhibitor (KT-5823), a Ras inhibitor (manumycin A), a dominant negative Ras mutant (RasN17), a protein kinase C-alpha (PKC-alpha) inhibitor (Ro 32-0432), and a phosphoinositide-3-OH-kinase (PI3K) inhibitor (LY 294002). Pretreatment of A549 cells with either manumycin A or GW 5074 attenuated YC-1-induced p44/42 MAPK activation. The YC-1-mediated increase in IKKalpha/beta activation and kappaB-luciferase activity were attenuated by GW 5074, a MAPK/ERK kinase (MEK) inhibitor (PD 98059), and an ERK2 inhibitor (AG 126). Furthermore, YC-1-induced COX-2 promoter activity was also inhibited by GW 5074, PD 98059, and AG 126. These results indicate that YC-1 might activate the sGC/cGMP/PKG pathway to elicit Ras/Raf-1/p44/42 MAPK activation, which in turn induces IKKalpha/beta and NF-kappaB activation, and ultimately causes COX-2 expression in A549 cells. Moreover, PKC-alpha and PI3K signal might be involved in YC-1-induced Raf-1 activation. ------>tmu_sno=None ------>sno=21722 ------>authors2=Chen BC ------>authors3=Weng CM ------>authors4=Lee WS ------>authors5=Lin CH ------>authors6= ------>authors6_c= ------>authors=Chang MS ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=??? ------>publish_area=0 ------>updateTitle=Involvement of Ras/Raf-1/p44/42 MAPK in YC-1-induced cyclooxygenase-2 expression in human pulmonary epithelial cells. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=4 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2009 ------>submit_flag=None ------>publish_month=10 |