Induction of Alzheimer-specific tau epitope AT100 in apoptotic human fetalastrocytes

Citation
H. Ksiezak-reding et al., Induction of Alzheimer-specific tau epitope AT100 in apoptotic human fetalastrocytes, CELL MOTIL, 47(3), 2000, pp. 236-252
Citations number
89
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL MOTILITY AND THE CYTOSKELETON
ISSN journal
0886-1544 → ACNP
Volume
47
Issue
3
Year of publication
2000
Pages
236 - 252
Database
ISI
SICI code
0886-1544(200011)47:3<236:IOATEA>2.0.ZU;2-B
Abstract
In Alzheimer's and other neurodegenerative diseases, hyperphosphorylated ta u accumulates in affected neuronal and glial cells in the form of paired he lical filaments (PHFs). This tau binds antibody AT100, which recognizes the double phosphorylation site (Thr212/Ser214) that is not present in normal biopsy tau. In primary cultures, highly enriched (>98%) in astrocytes of hu man fetal brain, three polypeptides of 52, 64, and 70 kD showed immunoreact ivity with tau antibodies against non-phosphorylated epitopes, accounting f or 88, 12, and <1%, respectively, of the total reactivity. All three polype ptides were phosphorylated at the PHF-1 epitope but not at the epitopes Tau -1, 12E8, AT8, and AT100. Treatment of cultures with okadaic acid resulted in apoptosis characterized by the blebbing of the plasma membrane, condensa tion of nuclear chromatin, and fragmentation of the nucleus. This treatment also resulted in a 3- to 5-fold increase in the content of both tau protei n and phosphorylation. The increases were observed in all phosphorylation s ites examined, and included the AT100 site. The AT100 site has been propose d to be generated by protein kinase B/Akt and Cdc2. Since okadaic acid can induce an AD-like hyperphosphorylated state of normal tau in primary cultur es of human brain cells, a simple cellular model is available permitting st udy of self-aggregation of tan and phosphorylation events characteristic of neurodegeneration. (C) 2000 Wiley-Liss, Inc.