| Yin KJ |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=33 ------>confirm_bywho=shiemin ------>insert_bywho=hsuc ------>Jurnal_Rank=None ------>authors4_c=None ------>comm_author=1 ------>patent_EDate=None ------>authors5_c=None ------>publish_day=None ------>paper_class2Letter=None ------>page2=2477 ------>medlineContent= ------>unit=E0123 ------>insert_date=20041201 ------>iam=5 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN=None ------>authors_c=None ------>score=285 ------>journal_name=Stroke ------>paper_name=ATM gene regulates OGD-induced NF-kB DNA-binding activity and downstream apoptotic cascade in mouse cerebrovascular endothelial cells. ------>confirm_date=20050628 ------>tch_id=091141 ------>pmid=12364740 ------>page1=2471 ------>fullAbstract=BACKGROUND AND PURPOSE: Cells lacking the ATM (ataxia telangectasia mutated) gene are hypersensitive to DNA damage caused by a variety of insults. ATM may regulate oxidative stress-induced signaling cascades involving nuclear factor-kappaB (NF-kappaB), a transcription factor that is upstream of a wide variety of stress-responsive genes. We investigated the potential interaction of ATM and NF-kappaB after oxygen-glucose deprivation (OGD) in cerebral endothelial cells (CECs). METHODS: Primary cultures of mouse CECs were subjected to OGD in the absence or presence of ATM antisense oligonucleotides or the NF-kappaB inhibitor SN50. ATM expression was determined with the use of reverse transcription-polymerase chain reaction and Western blot, and NF-kappaB activity was assessed by electrophoretic mobility shift assay. Cells were assessed for mitochondrial DNA damage with the use of long polymerase chain reaction and were assessed for caspase-3 and caspase-8 activity with the use of fluorogenic substrates. Cell death was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and LDH release. RESULTS: OGD stimulated ATM gene expression at the mRNA and protein level in CECs as early as 1 hour after OGD initiation. ATM gene knockdown with the use of an antisense oligonucleotide suppressed OGD-induced ATM protein expression, which was accompanied by an attenuation of NF-kappaB activation and the subsequent expression of downstream genes, including the antiapoptotic gene c-IAP2. ATM knockdown also accentuated OGD-induced mitochondrial DNA damage and the activation of caspase-3 and caspase-8, leading to enhanced CEC death. The specific NF-kappaB inhibitor SN50 mimicked the effects of ATM knockdown. CONCLUSIONS: We conclude that ATM may play a cytoprotective role in OGD-induced CEC death via a NF-kappaB-dependent signaling pathway. ------>tmu_sno=None ------>sno=10405 ------>authors2=Chen SD ------>authors3=Lee JM ------>authors4=Xu J ------>authors5=Hsu CY ------>authors6= ------>authors6_c=None ------>authors=Yin KJ ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=ATM gene regulates oxygen-glucose deprivation-induced nuclear factor-kappaB DNA-binding activity and downstream apoptotic cascade in mouse cerebrovascular endothelial cells. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2002 ------>submit_flag=None ------>publish_month=None |