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Mechanism of zinc‐induced phosphorylation of p70 S6 kinase and glycogen synthase kinase 3β in SH‐SY5Y neuroblastoma cells
Author(s) -
An WenLin,
Bjorkdahl Cecilia,
Liu Rong,
Cowburn Richard F.,
Winblad Bengt,
Pei JinJing
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02948.x
Subject(s) - gsk 3 , phosphorylation , p70 s6 kinase 1 , wortmannin , protein kinase b , kinase , ribosomal s6 kinase , chemistry , sh sy5y , microbiology and biotechnology , pi3k/akt/mtor pathway , map kinase kinase kinase , map2k7 , mapk/erk pathway , protein kinase a , ly294002 , cyclin dependent kinase 2 , biology , signal transduction , neuroblastoma , cell culture , genetics
We have previously reported an aberrant accumulation of activated protein kinase B (PKB), glycogen synthase kinase (GSK)‐3β, 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‐3β phosphorylation is unknown. In the current study, 100 μ m 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‐3β 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‐3β, 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‐3β is regulated by rapamycin‐dependent, PI3K and MAPK pathways. Furthermore, phosphorylation of p70S6K and GSK‐3β 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 μ m zinc might activate PKB, GSK‐3β, ERK1/2, JNK, p38 and p70S6K, that are consequently involved in tau changes in SH‐SY5Y cells.