| Ho, Pei-Yin |
------>authors3_c=??? ------>paper_class1=1 ------>Impact_Factor=3.846 ------>paper_class3=2 ------>paper_class2=1 ------>vol=229 ------>confirm_bywho=leehorng ------>insert_bywho=hoyuansn ------>Jurnal_Rank=8.2 ------>authors4_c=??? ------>comm_author= ------>patent_EDate=None ------>authors5_c=??? ------>publish_day=1 ------>paper_class2Letter=None ------>page2=93 ------>medlineContent= ------>unit=E0310 ------>insert_date=20080711 ------>iam=5 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c=??? ------>score=500 ------>journal_name=Toxicology and Applied Pharmacology ------>paper_name=Inhibition of the ERK phosphorylation plays a role in terbinafine-induced p21 up-regulation and DNA synthesis inhibition in human vascular endothelial cells ------>confirm_date=20081118 ------>tch_id=084007 ------>pmid=18272192 ------>page1=86 ------>fullAbstract=Previously, we showed that terbinafine (TB) induces cell-cycle arrest in cultured human umbilical vein endothelial cells (HUVEC) through an up-regulation of the p21 protein. The aim of this study is to delineate the molecular mechanisms underlying TB-induced increase of p21 protein. RT-PCR analysis demonstrated that the mRNA levels of p21 and p53 were increased in the TB-treated HUVEC. The p21 promoter activity was also increased by TB treatment. Transfection of HUVEC with p53 dominant negative (DN) abolished the TB-induced increases of p21 promoter activity and protein level, suggesting that the TB-induced increase of p21 is p53-dependent. Western blot analysis demonstrated that TB decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK). Over-expression of mitogen-activated protein kinase (MEK)-1, the immediate upstream activator kinase of ERK, abolished the TB-induced increases of p21 and p53 protein and decrease of thymidine incorporation. The ERK inhibitor (PD98059) enhanced the TB-induced inhibition of thymidine incorporation into HUVEC. Taken together, these data suggest that the decrease of ERK activity plays a role in the TB-induced up-regulation of p21 in HUVEC. On the other hand, pretreatment of the cells with geranylgeraniol (GGOH), farnesol (FOH), or Ras inhibitor peptide did not affect the TB-induced decrease of thymidine incorporation. Taken together, our results suggest that TB might cause a decrease of MEK, which in turn up-regulates p53 through the inhibition of ERK phosphorylation, and finally causes an increase of p21 expression and cell-cycle arrest. ------>tmu_sno=None ------>sno=18729 ------>authors2=Hsu Sung-Po ------>authors3=Liang, Yu-Chih ------>authors4=Kuo, Min-Liang ------>authors5=Ho, Yuan-Soo ------>authors6=Lee, Wen-Sen ------>authors6_c=??? ------>authors=Ho, Pei-Yin ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=??? ------>publish_area=0 ------>updateTitle=Inhibition of the ERK phosphorylation plays a role in terbinafine-induced p21 up-regulation and DNA synthesis inhibition in human vascular endothelial cells. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2008 ------>submit_flag=None ------>publish_month=1 |