Overexpression of tau leads to the stimulation of neurite outgrowth, the activation of caspase 3 activity, and accumulation and phosphorylation of tau in neuroblastoma cells on cAMP treatment.
To explore changes to the tau molecule in Alzheimer's disease, we studied the effect of tau expression in stably transfected neuroblastoma x glioma hybrid NG108-15 cells (tau cells). Tau cells had a similar shape to, but more neurites than, wild type NG108-15 cells (wild type cells). When treated with cAMP, tau cells began to form neurites within 2h. After that, these neurites became longer and thicker than those of wild type cells. An accumulation and increased phosphorylation of tau were observed after 8 h and caspase 3 activity was increased after 4 h in tau cells, but not in wild type cells, upon treatment with cAMP. Caspase 3 activity was activated after the initiation of morphological change, and before the accumulation of tau in tau cells. Under these conditions, apoptotic cell death was not observed and tau was colocalized with tubulin. However, the accumulated tau molecules did not associate with tubulin and were dislocated around and in the nuclei of tau cells. These observations have implications for the cellular causes of Alzheimer's disease where the accumulation and mislocation of tau occur concomitant with neuronal degeneration.
Yoshizaki
Chihiro
C
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Shomachi 1, Tokushima 770-8505, Japan.
Tsukane
Mariko
M
Yamauchi
Takashi
T
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D000242:Cyclic AMP / Q000494:pharmacology* / Q000627:therapeutic use; D004789:Enzyme Activation; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014404:Tubulin; D016875:tau Proteins; D010769:Phosphothreonine; D010768:Phosphoserine; D000242:Cyclic AMP; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases