学术探索
学术期刊
新闻热点
数据分析
智能评审

The effects of clozapine on the GSK-3-mediated signaling pathway

被引：107
作者：
Kang, UG
Seo, MS
Roh, MS
Kim, Y
Yoon, SC
Kim, YS
机构：
[1] Seoul Natl Univ, Coll Med, Dept Psychiat & Behav Sci, Seoul 110799, South Korea
[2] Seoul Natl Univ, Inst Neurosci, Seoul 110799, South Korea
[3] Seoul Natl Univ Hosp, Clin Res Inst, Seoul 110744, South Korea
[4] Kangwon Natl Univ, Coll Med, Dept Neuropsychiat, Chunchon, South Korea
来源：
FEBS LETTERS | 2004年 / 560卷 / 1-3期
关键词：
clozapine; glycogen synthase kinase-3 beta; Dvl; Wnt; phosphatidylinositol; 3-kinase;
D O I：
10.1016/S0014-5793(04)00082-1
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We investigated the effect of 10 muM clozapine on the activity of glycogen synthase kinase-3beta (GSK-3beta) and its upstream and downstream molecules in SH-SY5Y human neuro-blascoma cells. Clozapine activates both Akt- and Dvl-mediated phosphorylation of GSK-3beta through phosphorylation at Ser9, and increased total cellular and intranuclear levels of beta-catenin. Pretreatment with the specific inhibitor of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, LY294002 (20 muM), prevented the phosphorylation of Akt but did not affect the phosphorylation of GSK-3beta. These results suggest that clozapine regulates the phosphorylation of GSK-3beta through Wnt signal pathways involving Dvl upstream but not through the PI3K-Akt pathway in SFI-SY5Y cells. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：115 / 119
页数：5
相关论文
共 21 条
[1]   Nuclear endpoint of Wnt signaling: Neoplastic transformation induced by transactivating lymphoid-enhancing factor 1 [J].
Aoki, M ;
Hecht, A ;
Kruse, U ;
Kemler, R ;
Vogt, PK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (01) :139-144
[2]  
Bournat JC, 2000, J NEUROSCI RES, V61, P21, DOI 10.1002/1097-4547(20000701)61:1<21::AID-JNR3>3.3.CO
[3]  
2-Z
[4]   Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons [J].
Chalecka-Franaszek, E ;
Chuang, DM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (15) :8745-8750
[5]   The mood-stabilizing agent valproate inhibits the activity of glycogen synthase kinase-3 [J].
Chen, G ;
Huang, LD ;
Jiang, YM ;
Manji, HK .
JOURNAL OF NEUROCHEMISTRY, 1999, 72 (03) :1327-1330
[6]   Clozapine in treatment-resistant patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder: A naturalistic 48-month follow-up study [J].
Ciapparelli, A ;
Dell'Osso, L ;
di Poggio, AB ;
Carmassi, C ;
Cecconi, D ;
Fenzi, M ;
Chiavacci, MC ;
Bottai, M ;
Ramacciotti, CE ;
Cassano, GB .
JOURNAL OF CLINICAL PSYCHIATRY, 2003, 64 (04) :451-458
[7]   The renaissance of GSK3 [J].
Cohen, P ;
Frame, S .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2001, 2 (10) :769-776
[8]   INHIBITION OF GLYCOGEN-SYNTHASE KINASE-3 BY INSULIN-MEDIATED BY PROTEIN-KINASE-B [J].
CROSS, DAE ;
ALESSI, DR ;
COHEN, P ;
ANDJELKOVICH, M ;
HEMMINGS, BA .
NATURE, 1995, 378 (6559) :785-789
[9]   Regulation of Akt and glycogen synthase kinase-3β phosphorylation by sodium valproate and lithium [J].
De Sarno, P ;
Li, XH ;
Jope, RS .
NEUROPHARMACOLOGY, 2002, 43 (07) :1158-1164
[10]   Differential regulation of glycogen synthase kinase 3β by insulin and Wnt signaling [J].
Ding, VW ;
Chen, RH ;
McCormick, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (42) :32475-32481
123