Hsu HK, Juan SH, Ho PY, Liang YC, Lin CH, Teng CM and Lee WS |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=66 ------>confirm_bywho=chlin ------>insert_bywho=chlin ------>Jurnal_Rank=None ------>authors4_c=None ------>comm_author= ------>patent_EDate=None ------>authors5_c=None ------>publish_day=None ------>paper_class2Letter=None ------>page2=271 ------>medlineContent= ------>unit=E0200 ------>insert_date=20030430 ------>iam=5 ------>update_date= ------>author=??? ------>change_event=4 ------>ISSN=None ------>authors_c=None ------>score=500 ------>journal_name=Biochem. Pharmacol. ------>paper_name=YC-1 inhibits proliferation of human vascular endothelial cells through a cyclic GMP-independent pathway ------>confirm_date=20050401 ------>tch_id=085007 ------>pmid=12826268 ------>page1=263 ------>fullAbstract=This study was designed to investigate the effect of YC-1, 3-(5~-hydroxymethyl-2~-furyl)-1-benzylindazole, in human umbilical vein endothelial cells (HUVECs) proliferation and its underlying mechanism. YC-1 at a range of concentrations (5-50 microM) inhibited DNA synthesis and decreased cell number in cultured HUVEC in a dose- and time-dependent manner. YC-1 was not cytotoxic at these concentrations. [3H]thymidine incorporation and flow cytometry analyses revealed that YC-1 treatment decreased DNA synthesis and arrested the cells at the G0/G1 phase of the cell cycle. Western blot analysis demonstrated that YC-1 (5-50 microM) increased the levels of cyclin-dependent kinase (CDK)-inhibitory proteins (CKIs), p21 and p27, but did not induce any significant changes of cyclins and CDKs. In the YC-1-treated HUVEC, the formation of CDK2-p21 complex, but not CDK2-p27 complex, was increased and the assayable CDK2 kinase activity was decreased. These changes were in a dose-dependent manner. In contrast, the formations of CDK4-p21 and CDK4-p27 complex were slightly increased and the assayable CDK4 kinase activity was slightly decreased (if there were any changes). Pretreatment with guanylyl cyclase inhibitors, 1H-(1,2,4)oxadiazolo[4,3-a]quinozalin-1-one (ODQ) and methylene blue, inhibited the YC-1-induced increase of cyclic GMP level, but did not change significantly the magnitude of the YC-1-induced inhibition of thymidine incorporation and cell number in HUVEC. These results indicate that YC-1-induced cell cycle arrest in HUVEC occurred when the cyclin-CDK system was inhibited just as p21 and p27 protein levels were augmented. This YC-1-induced antiproliferation effect in HUVEC is via a cyclic GMP-independent pathway. ------>tmu_sno=None ------>sno=7169 ------>authors2= ------>authors3= ------>authors4= ------>authors5= ------>authors6= ------>authors6_c=None ------>authors=Hsu HK, Juan SH, Ho PY, Liang YC, Lin CH, Teng CM and Lee WS ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=YC-1 inhibits proliferation of human vascular endothelial cells through a cyclic GMP-independent pathway. ------>language=2 ------>check_flag= ------>submit_date= ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho= ------>publish_year=2003 ------>submit_flag= ------>publish_month=None |