title: Ca2+/calmodulin-dependent protein kinase II mediates apoptosis of P19 cells expressing human tau during neural differentiation with retinoic acid treatment.
abstract: The involvement of tau phosphorylation in apoptosis resembling Alzheimer's disease (AD) was investigated using a cell model of P19 cells stably expressing human tau441 (tau/P19 cells). Apoptotic cell death was observed specifically in tau/P19 cells during neural differentiation with retinoic acid (RA) treatment. A CaM kinase II inhibitor, KN-93, protected tau/P19 cells from apoptosis, although it stimulated the cell death of wild-type P19 cells (wt/P19 cells). W-7 and calmidazolium, calmodulin antagonists, also specifically inhibited the apoptosis of tau/P19 cells. LiCl, an inhibitor of glycogen synthase 3, a tau kinase, was effective in protecting tau/P19 cells from apoptosis, but the protective effect was less than that of CaM kinase II inhibitor and calmodulin antagonists. Tau in the nuclei of tau/P19 cells was phosphorylated at the sites for CaM kinase II detected by an antibody recognizing a phosphorylated form of tau. These results indicated that CaM kinase II was involved in the apoptosis of tau/P19 cells induced by RA treatment.
authors.affiliation: Department of Biochemistry, Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, University of Tokushima, Tokushima, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Tsukane
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamauchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D016875:tau Proteins / Q000378:metabolism*; D000096926:Benzenesulfonamides
chemical_list: D000970:Antineoplastic Agents; D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D013449:Sulfonamides; D014212:Tretinoin; D016875:tau Proteins; C072105:KN 93; D000096926:Benzenesulfonamides