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Mechanism of zinc-induced phosphorylation of p70 S6 kinase and glycogen synthase kinase 3beta in SH-SY5Y neuroblastoma cells.
J Neurochem. 2005 Mar; 92(5):1104-15.JN

Abstract

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 microM 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 microM zinc might activate PKB, GSK-3beta, ERK1/2, JNK, p38 and p70S6K, that are consequently involved in tau changes in SH-SY5Y cells.

Authors+Show Affiliations

An WL
Division of Experimental Geriatrics, Karolinska Institutet, Huddinge, Sweden.
Bjorkdahl C
No affiliation info available
Liu R
No affiliation info available
Cowburn RF
No affiliation info available
Winblad B
No affiliation info available
Pei JJ
No affiliation info available

MeSH

Analysis of VarianceAnimalsAntibiotics, AntineoplasticBlotting, WesternBrainCell Line, TumorCell SurvivalCulture Media, Serum-FreeCytoplasmDose-Response Relationship, DrugDrug InteractionsEnzyme InhibitorsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansImmunohistochemistryIn Vitro TechniquesMicroscopy, ImmunoelectronModels, BiologicalNeuroblastomaPhosphorylationRatsRibosomal Protein S6 Kinases, 70-kDaSirolimusTetrazolium SaltsThiazolesTime FactorsZincZinc Sulfaterab5 GTP-Binding Proteinstau Proteins

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15715661

Citation

An, Wen-Lin, et al. "Mechanism of Zinc-induced Phosphorylation of P70 S6 Kinase and Glycogen Synthase Kinase 3beta in SH-SY5Y Neuroblastoma Cells." Journal of Neurochemistry, vol. 92, no. 5, 2005, pp. 1104-15.
An WL, Bjorkdahl C, Liu R, et al. Mechanism of zinc-induced phosphorylation of p70 S6 kinase and glycogen synthase kinase 3beta in SH-SY5Y neuroblastoma cells. J Neurochem. 2005;92(5):1104-15.
An, W. L., Bjorkdahl, C., Liu, R., Cowburn, R. F., Winblad, B., & Pei, J. J. (2005). Mechanism of zinc-induced phosphorylation of p70 S6 kinase and glycogen synthase kinase 3beta in SH-SY5Y neuroblastoma cells. Journal of Neurochemistry, 92(5), 1104-15.
An WL, et al. Mechanism of Zinc-induced Phosphorylation of P70 S6 Kinase and Glycogen Synthase Kinase 3beta in SH-SY5Y Neuroblastoma Cells. J Neurochem. 2005;92(5):1104-15. PubMed PMID: 15715661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanism of zinc-induced phosphorylation of p70 S6 kinase and glycogen synthase kinase 3beta in SH-SY5Y neuroblastoma cells. AU - An,Wen-Lin, AU - Bjorkdahl,Cecilia, AU - Liu,Rong, AU - Cowburn,Richard F, AU - Winblad,Bengt, AU - Pei,Jin-Jing, PY - 2005/2/18/pubmed PY - 2005/4/29/medline PY - 2005/2/18/entrez SP - 1104 EP - 15 JF - Journal of neurochemistry JO - J Neurochem VL - 92 IS - 5 N2 - 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 microM 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 microM zinc might activate PKB, GSK-3beta, ERK1/2, JNK, p38 and p70S6K, that are consequently involved in tau changes in SH-SY5Y cells. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/15715661/Mechanism_of_zinc_induced_phosphorylation_of_p70_S6_kinase_and_glycogen_synthase_kinase_3beta_in_SH_SY5Y_neuroblastoma_cells_ DB - PRIME DP - Unbound Medicine ER -