Lee JT |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=164 ------>confirm_bywho=ryyuan ------>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=131 ------>medlineContent= ------>unit=E0100 ------>insert_date=20050701 ------>iam=7 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN=None ------>authors_c=None ------>score=500 ------>journal_name=J Cell Biol ------>paper_name=Amyloid-beta peptide induces oligodendrocyte death by activating the neutral sphingomyelinase-ceramide pathway. ------>confirm_date=20050711 ------>tch_id=091141 ------>pmid=14709545 ------>page1=123 ------>fullAbstract=Amyloid-beta peptide (Abeta) accumulation in senile plaques, a pathological hallmark of Alzheimer~s disease (AD), has been implicated in neuronal degeneration. We have recently demonstrated that Abeta induced oligodendrocyte (OLG) apoptosis, suggesting a role in white matter pathology in AD. Here, we explore the molecular mechanisms involved in Abeta-induced OLG death, examining the potential role of ceramide, a known apoptogenic mediator. Both Abeta and ceramide induced OLG death. In addition, Abeta activated neutral sphingomyelinase (nSMase), but not acidic sphingomyelinase, resulting in increased ceramide generation. Blocking ceramide degradation with N-oleoyl-ethanolamine exacerbated Abeta cytotoxicity; and addition of bacterial sphingomyelinase (mimicking cellular nSMase activity) induced OLG death. Furthermore, nSMase inhibition by 3-O-methyl-sphingomyelin or by gene knockdown using antisense oligonucleotides attenuated Abeta-induced OLG death. Glutathione (GSH) precursors inhibited Abeta activation of nSMase and prevented OLG death, whereas GSH depletors increased nSMase activity and Abeta-induced death. These results suggest that Abeta induces OLG death by activating the nSMase-ceramide cascade via an oxidative mechanism. ------>tmu_sno=None ------>sno=11523 ------>authors2=Xu J ------>authors3=Lee JM ------>authors4=Han X ------>authors5=Yang DI ------>authors6=Chen S, Hsu CY ------>authors6_c=None ------>authors=Lee JT ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=Amyloid-beta peptide induces oligodendrocyte death by activating the neutral sphingomyelinase-ceramide pathway. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=1 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2004 ------>submit_flag=None ------>publish_month=None |