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The involvement of glycogen synthase kinase-3 and protein phosphatase-2A in lactacystin-induced tau accumulation

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成果类型:
期刊论文
作者:
Ren, QG;Liao, XM;Wang, ZF;Qu, ZS;Wang, JZ*
通讯作者:
Wang, JZ
作者机构:
[Wang, JZ] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pathophysiol, Key Lab Neurol Dis, Wuhan 430030, Hubei Province, Peoples R China.
Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.
通讯机构:
[Wang, JZ] H
Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pathophysiol, Key Lab Neurol Dis, Wuhan 430030, Hubei Province, Peoples R China.
语种:
英文
关键词:
Proteasome;Tau;Hyperphosphorylation;Glycogen synthase kinase-3;Protein phosphatase-2A
期刊:
FEBS Letters
ISSN:
0014-5793
年:
2006
卷:
580
期:
10
页码:
2503-2511
基金类别:
We thank Drs. Iqbal K. and Grundke-Iqbal I. from NYS Institute for Basic Research for antibody R134d. We also thank Dr. Davies P. from Albert Einstein College of Medicine, Bronx, NY, USA for antibody PHF-1. This work was supported in part by grants from National Major Grant for Basic Research (2006CB500703) and the National Natural Science Foundation of China (32328007 and 30430270).
机构署名:
本校为其他机构
院系归属:
生命科学学院
摘要:
Here, we demonstrated that lactacystin inhibited proteasome dose-dependently in HEK293 cells stably expressing tau. Simultaneously, it induces accumulation of both non-phosphorylated and hyperphosphorylated tau and decreases the binding of tau to the taxol-stabilized microtubules. Lactacystin activates glycogen synthase kinsase-3 (GSK-3) and decreases the phosphorylation of GSK-3 at serine-9. LiCl inhibits GSK-3 and thus reverses the lactacystin-induced accumulation of the phosphorylated tau. Lactacystin also inhibits protein phosphase-2A (PP-2...

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