Effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell culture | |
Wang, Ze-Fen ; Li, Hong-Lian ; Li, Xia-Chun ; Zhang, Qi ; Tian, Qing ; Wang, Qun ; Xu, Huaxi ; Wang, Jian-Zhi ; Xu HX(许华曦) | |
刊名 | http://dx.doi.org/10.1111/j.1471-4159.2006.03956.x |
2006-08 | |
关键词 | GLYCOGEN-SYNTHASE KINASE-3-BETA CYCLIN-DEPENDENT KINASE-5 PRECURSOR PROTEIN ALZHEIMERS-DISEASE HIPPOCAMPAL-NEURONS TRANSGENIC MICE ACTIVATION CDK5 PRESENILIN-1 INHIBITION |
英文摘要 | Alzheimer's disease is characterized by beta-amyloid (A beta) overproduction and tau hyperphosphorylation. Recent studies have shown that synthetic A beta promotes tau phosphorylation in vitro. However, whether endogenously overproduced A beta promotes tau phosphorylation and the underlying mechanisms remain unknown. Here, we used mouse neuroblastoma N2a stably expressing wild-type amyloid precursor protein (APPwt) or the Swedish mutant APP (APPswe) to determine the alterations of phosphorylated tau and the related protein kinases. We found that phosphorylation of tau at paired helical filament (PHF)-1, pSer396 and pThr231 epitopes was significantly increased in cells transfected with APPwt and APPswe, which produced higher levels of A beta than cells transfected with vector or amyloid precursor-like protein 1. The activity of glycogen synthase kinase-3 (GSK-3) was up-regulated with a concomitant reduction in the inhibitory phosphorylation of GSK-3 at its N-terminal Ser9 residue. In contrast, the activity of cyclin-dependent kinase-5 (CDK-5) and protein kinase C (PKC) was down-regulated. Inhibition of GSK-3 by LiCl, but not inhibition of CDK-5 by roscovitine, arrested A beta secretion and tau phosphorylation. Inhibition of PKC by GF-109203X activated GSK-3, whereas activation of PKC by phorbol-12,13-dibutyrate inhibited GSK-3. These results suggest that endogenously overproduced A beta induces increased tau phosphorylation through activation of GSK-3, and that inactivation of PKC is at least one of the mechanisms involved in GSK-3 activation. |
语种 | 英语 |
出版者 | J NEUROCHEM |
内容类型 | 期刊论文 |
源URL | [http://dspace.xmu.edu.cn/handle/2288/93312] |
专题 | 医学院-已发表论文 |
推荐引用方式 GB/T 7714 | Wang, Ze-Fen,Li, Hong-Lian,Li, Xia-Chun,et al. Effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell culture[J]. http://dx.doi.org/10.1111/j.1471-4159.2006.03956.x,2006. |
APA | Wang, Ze-Fen.,Li, Hong-Lian.,Li, Xia-Chun.,Zhang, Qi.,Tian, Qing.,...&许华曦.(2006).Effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell culture.http://dx.doi.org/10.1111/j.1471-4159.2006.03956.x. |
MLA | Wang, Ze-Fen,et al."Effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell culture".http://dx.doi.org/10.1111/j.1471-4159.2006.03956.x (2006). |
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