Mechanism of zinc-induced phosphorylation of p70 S6 kinase and glycogen synthase kinase 3β in SH-SY5Y neuroblastoma cells

被引:87
作者
An, WL
Bjorkdahl, C
Liu, R
Cowburn, RF
Winblad, B
Pei, JJ
机构
[1] Karolinska Inst, Dept Neurotec, Div Expt Geriatr, Novum, S-14186 Huddinge, Sweden
[2] Karolinska Inst, Dept Neurotec, Sumitomo Pharmaceut Alzheimer Ctr, KASPEC, S-14186 Huddinge, Sweden
关键词
Alzheimer's disease; glycogen synthase kinase 3 beta; mitogen-activated protein kinase; p70; S6; kinase; phosphatidylinositol; 3-kinase; zinc;
D O I
10.1111/j.1471-4159.2004.02948.x
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 have previously reported an aberrant accumulation of activated protein kinase B (PKB), glycogen synthase kinase (GSK)-3beta, extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), p38 and p70 S6 kinase (p70S6K) in neurons bearing neurofibrillary tangles (NFTs) in Alzheimer's disease (AD). However, the mechanism by which these tau candidate kinases are involved in the regulation of p70S6K and GSK-3beta phosphorylation is unknown. In the current study, 100 muM zinc sulfate was used, and influences of various components of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways on p70S6K and GSK-3beta phosphorylation have been investigated in serum-deprived SH-SY5Y neuroblastoma cells. We found that zinc could induce an increase of phosphorylated (p) p70S6K, p-PKB, p-GSK-3beta, p-ERK1/2, p-JNK and p-p38, especially in long-term treatment (4-8 h). Treatment with different inhibitors including rapamycin, wortmannin, LY294002, and U0126, and their combinations, indicated that phosphorylation of p70S6K and GSK-3beta is regulated by rapamycin-dependent, PI3K and MAPK pathways. Furthermore, phosphorylation of p70S6K and GSK-3beta affected levels of tau unphosphorylated at the Tau-1 site and phosphorylated at the PHF-1 site, and p70S6K phosphorylation affected the total tau level. Thus, 100 muM zinc might activate PKB, GSK-3beta, ERK1/2, JNK, p38 and p70S6K, that are consequently involved in tau changes in SH-SY5Y cells.
引用
收藏
页码:1104 / 1115
页数:12
相关论文
共 50 条
[21]  
Hosoi H, 1999, CANCER RES, V59, P886
[22]   The endogenous and cell cycle-dependent phosphorylation of tau protein in living cells:: Implications for Alzheimer's disease [J].
Illenberger, S ;
Zheng-Fischhöfer, QY ;
Preuss, U ;
Stamer, K ;
Baumann, K ;
Trinczek, B ;
Biernat, J ;
Godemann, R ;
Mandelkow, EM ;
Mandelkow, E .
MOLECULAR BIOLOGY OF THE CELL, 1998, 9 (06) :1495-1512
[23]  
JOHNSON GVW, 1996, RECENT RES DEV NEURO, V1, P89
[24]   Extracellular zinc activates p70 S6 kinase through the phosphatidylinositol 3-kinase signaling pathway [J].
Kim, S ;
Jung, Y ;
Kim, D ;
Koh, H ;
Chung, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (34) :25979-25984
[25]   Akt/PKB kinase phosphorylates separately Thr212 and Ser214 of tau protein in vitro [J].
Ksiezak-Reding, H ;
Pyo, HK ;
Feinstein, B ;
Pasinetti, GM .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2003, 1639 (03) :159-168
[26]   Farnesyltransferase inhibitor induces rapid growth arrest and blocks p70s6k activation by multiple stimuli [J].
Law, BK ;
Norgaard, P ;
Moses, HL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (15) :10796-10801
[27]   Neurodegenerative tauopathies [J].
Lee, VMY ;
Goedert, M ;
Trojanowski, JQ .
ANNUAL REVIEW OF NEUROSCIENCE, 2001, 24 :1121-1159
[28]   Insulin transiently increases tau phosphorylation:: Involvement of glycogen synthase kinase-3β and Fyn tyrosine kinase [J].
Lesort, M ;
Jope, RS ;
Johnson, GVW .
JOURNAL OF NEUROCHEMISTRY, 1999, 72 (02) :576-584
[29]   Decreased nuclear β-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3β conditional transgenic mice [J].
Lucas, JJ ;
Hernández, F ;
Gómez-Ramos, P ;
Morán, MA ;
Hen, R ;
Avila, J .
EMBO JOURNAL, 2001, 20 (1-2) :27-39
[30]   Synthesis of the translational apparatus is regulated at the translational level [J].
Meyuhas, O .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2000, 267 (21) :6321-6330