| Ho FM |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=4.741 ------>paper_class3=2 ------>paper_class2=1 ------>vol=18 ------>confirm_bywho=chshih43 ------>insert_bywho=bcchen ------>Jurnal_Rank=24.5 ------>authors4_c=None ------>comm_author= ------>patent_EDate=None ------>authors5_c=None ------>publish_day=1 ------>paper_class2Letter=None ------>page2=399 ------>medlineContent= ------>unit=E0400 ------>insert_date=20060207 ------>iam=3 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c=None ------>score=469 ------>journal_name=Cellular Signaling ------>paper_name=High glucose-induced apoptosis in human vascular endothelial cells is mediated through NF-kB and c-Jun NH2-terminal kinase pathway and prevented by PI3K/Akt/eNOS pathway. ------>confirm_date=20060208 ------>tch_id=091057 ------>pmid=15970429 ------>page1=391 ------>fullAbstract=Our previous studies demonstrated that high glucose-induced apoptosis in human umbilical vein endothelial cells (HUVECs) is mediated by sequential activation of c-Jun N-terminal kinase (JNK) and caspase, and prevented by exogenous nitric oxide (NO). In this study we further elucidated the roles of the transcriptional factor NF-kappaB, phosphatidylinositol 3~-kinase (PI3K), Akt and endothelial nitric oxide synthase (eNOS) in the apoptosis of HUVECs induced by high glucose. The results showed that high glucose-induced apoptosis was significantly enhanced by PI3K inhibitors (wortmannin and LY294002), NOS inhibitor (NG-nitro-arginine methyl ester) and eNOS antisense oligonucleotide. In contrast, apoptosis was markedly reduced by NF-kappaB inhibitor (pyrrolidine dithiocarbamate, PDTC), NF-kappaB antisense oligonucleotide, NO donor (sodium nitroprusside, SNP), and overexpression of Akt. The high glucose-induced NF-kappaB activation and transient Akt phosphorylation were prevented by the presence of vitamin C. Moreover, high glucose-induced increase in eNOS expression was attenuated by PI3K inhibitors and the negative mutant of PI3K. The activity of JNK induced by high glucose was suppressed by NF-kappaB-specific antisense oligonucleotide. Taken together our results demonstrated that high glucose-induced HUVECs apoptosis is through NF-kappaB-dependent JNK activation and reactive oxygen species (ROS)-dependent Akt dephosphorylation. Activation of the ROS/PI3K/Akt/eNOS signaling pathway in early phase exerts protective effects against the induction of apoptosis by high glucose. ------>tmu_sno=None ------>sno=12599 ------>authors2=Lin WW ------>authors3=Chen BC ------>authors4=Chao CM ------>authors5=Yang CR ------>authors6=Lin LY, Lai CC, Liu SH, Liau CS ------>authors6_c=None ------>authors=Ho FM ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=0 ------>updateTitle=High glucose-induced apoptosis in human vascular endothelial cells is mediated through NF-kappaB and c-Jun NH2-terminal kinase pathway and prevented by PI3K/Akt/eNOS pathway. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=2006 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2006 ------>submit_flag=None ------>publish_month=1 |