Abstract
In Alzheimer's and other neurodegenerative diseases, hyperphosphorylated tau accumulates in affected neuronal and glial cells in the form of paired helical 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 human fetal brain, three polypeptides of 52, 64, and 70 kD showed immunoreactivity with tau antibodies against non-phosphorylated epitopes, accounting for 88, 12, and <1%, respectively, of the total reactivity. All three polypeptides 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, condensation 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 protein and phosphorylation. The increases were observed in all phosphorylation sites examined, and included the AT100 site. The AT100 site has been proposed 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 cultures of human brain cells, a simple cellular model is available permitting study of self-aggregation of tau and phosphorylation events characteristic of neurodegeneration. (C) 2000 Wiley-Liss, Inc.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 236-252 |
| Number of pages | 17 |
| Journal | Cell Motility and the Cytoskeleton |
| Volume | 47 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2000 |
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Keywords
- Alzheimer's disease
- Apoptosis
- Okadaic acid
- Primary cultures
- Tau phosphorylation
- Tau protein
ASJC Scopus subject areas
- Cell Biology
Cite this
Induction of Alzheimer-specific tau epitope AT100 in apoptotic human fetal astrocytes. / Ksiezak-Reding, Hanna; He, Deke; Gordon-Krajcer, Wanda; Kress, Yvonne; Lee, Sunhee; Dickson, Dennis W.
In: Cell Motility and the Cytoskeleton, Vol. 47, No. 3, 2000, p. 236-252.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induction of Alzheimer-specific tau epitope AT100 in apoptotic human fetal astrocytes
AU - Ksiezak-Reding, Hanna
AU - He, Deke
AU - Gordon-Krajcer, Wanda
AU - Kress, Yvonne
AU - Lee, Sunhee
AU - Dickson, Dennis W.
PY - 2000
Y1 - 2000
N2 - In Alzheimer's and other neurodegenerative diseases, hyperphosphorylated tau accumulates in affected neuronal and glial cells in the form of paired helical 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 human fetal brain, three polypeptides of 52, 64, and 70 kD showed immunoreactivity with tau antibodies against non-phosphorylated epitopes, accounting for 88, 12, and <1%, respectively, of the total reactivity. All three polypeptides 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, condensation 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 protein and phosphorylation. The increases were observed in all phosphorylation sites examined, and included the AT100 site. The AT100 site has been proposed 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 cultures of human brain cells, a simple cellular model is available permitting study of self-aggregation of tau and phosphorylation events characteristic of neurodegeneration. (C) 2000 Wiley-Liss, Inc.
AB - In Alzheimer's and other neurodegenerative diseases, hyperphosphorylated tau accumulates in affected neuronal and glial cells in the form of paired helical 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 human fetal brain, three polypeptides of 52, 64, and 70 kD showed immunoreactivity with tau antibodies against non-phosphorylated epitopes, accounting for 88, 12, and <1%, respectively, of the total reactivity. All three polypeptides 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, condensation 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 protein and phosphorylation. The increases were observed in all phosphorylation sites examined, and included the AT100 site. The AT100 site has been proposed 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 cultures of human brain cells, a simple cellular model is available permitting study of self-aggregation of tau and phosphorylation events characteristic of neurodegeneration. (C) 2000 Wiley-Liss, Inc.
KW - Alzheimer's disease
KW - Apoptosis
KW - Okadaic acid
KW - Primary cultures
KW - Tau phosphorylation
KW - Tau protein
UR - http://www.scopus.com/inward/record.url?scp=0033744467&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033744467&partnerID=8YFLogxK
U2 - 10.1002/1097-0169(200011)47:3<236::AID-CM6>3.0.CO;2-K
DO - 10.1002/1097-0169(200011)47:3<236::AID-CM6>3.0.CO;2-K
M3 - Article
C2 - 11056524
AN - SCOPUS:0033744467
VL - 47
SP - 236
EP - 252
JO - Cytoskeleton
JF - Cytoskeleton
SN - 1949-3584
IS - 3
ER -