title: Zinc induces neurofilament phosphorylation independent of p70 S6 kinase in N2a cells.
abstract: Hyperphosphorylated neurofilaments are a part of neurofibrillary tangles in Alzheimer's disease brains. Zinc has been shown to be increased in the brain areas heavily affected by Alzheimer pathologies. Zinc could induce tau hyperphosphorylation in SH-SY5Y and N2a cells, and tau phosphorylation may be mediated by p70 S6 kinase activation. Many of the tau kinases can also phosphorylate neurofilaments, and in this study we wanted to see whether neurofilament phosphorylation is regulated by p70 S6 kinase in N2a cells. We found that zinc induces rapamycin-dependent p70 S6 kinase phosphorylation at Thr421/Ser424 and Thr389, and rapamycin-independent phosphorylation of neurofilaments at the SMI34 epitope. Although zinc could induce cell proliferation and cell growth, and increased phosphorylation of neurofilaments, only cell growth appeared to be related to p7056kinase activation.
authors.affiliation: Division of Experimental Geriatrics, Department of Neurotec, Karolinska Institutet, S-141 86 Huddinge, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Björkdahl
authors.forename: Magnus J
authors.initials: MJ
authors.lastname: Sjögren
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Jin-Jing
authors.initials: JJ
authors.lastname: Pei
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma; D016900:Neurofilament Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D016895:Culture Media, Serum-Free; D016900:Neurofilament Proteins; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D015032:Zinc; D020123:Sirolimus