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Titolo:
Proapoptotic effects of Tau cleavage product generated by caspase-3
Autore:
Chung, CW; Song, YH; Kim, IK; Yoon, WJ; Ryu, BR; Jo, DG; Woo, HN; Kwon, YK; Kim, HH; Gwag, BJ; Mook-Jung, IH; Jung, YK;
Indirizzi:
Kwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea Kwangju Inst Sci & Technol Kwangju South Korea 500712 00712, South Korea Natl Inst Hlth, Biomed Brain Res Ctr, Kwangju 500712, South Korea Natl Inst Hlth Kwangju South Korea 500712 r, Kwangju 500712, South Korea Ajou Univ, Sch Med, Dept Pharmacol, Suwon 441749, Kyungkido, South Korea Ajou Univ Suwon Kyungkido South Korea 441749 1749, Kyungkido, South Korea
Titolo Testata:
NEUROBIOLOGY OF DISEASE
fascicolo: 1, volume: 8, anno: 2001,
pagine: 162 - 172
SICI:
0969-9961(200102)8:1<162:PEOTCP>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; PAIRED HELICAL FILAMENT; ICE-LIKE PROTEASE; ALZHEIMERS-DISEASE; CELL-DEATH; IN-VITRO; INTERLEUKIN-1-BETA-CONVERTING ENZYME; MICROTUBULE-BINDING; ICE/CED-3 PROTEASE; NEURONAL CASPASE-3;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Jung, YK Kwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea Kwangju Inst Sci & Technol Kwangju South Korea 500712 uth Korea
Citazione:
C.W. Chung et al., "Proapoptotic effects of Tau cleavage product generated by caspase-3", NEUROBIOL D, 8(1), 2001, pp. 162-172

Abstract

Using an in vitro translation assay to screen a human brain cDNA library, we isolated the microtubule-associated protein Tau and determined it to be a caspase-3 substrate whose C-terminal cleavage occurred during neuronal apoptosis. Delta Tau, the 50-kDa cleavage product, was detected by Western blot in apoptotic cortical cells probed with anti-PHF-1 and anti-Tau-5 antibodies, but not anti-T-46 antibody which recognizes the C-terminus, Overexpression of Delta Tau in SK-N-BE2(C) cells significantly increased the incidence of cell death. Staurosporine-induced Tau cleavage was blocked by 20 muM z-Asp-Glu-Val-Asp-chloromethylketone, a caspase-3 inhibitor, and in vitro, Tau was selectively cleaved by caspase-3 or calpain, a calcium-activated protease, but not by caspases-1, -8, or -9. (D421E)-Tau, a mutant in which Asp421 was replaced with a Glu, was resistant to cleavage by caspase-3 and tended to suppress staurosporine-induced cell death more efficiently than didwildtype Tau in both transient and stable expression systems. Finally, theincidence of Delta Tau-induced cell death was augmented by expression of Abeta precursor protein (APP) or Swedish APP mutant. Taken together, these results suggest that the caspase-3 cleavage product of Tau may contribute to the progression of neuronal cell death in Alzheimer's disease. (C) 2001 Academic Press.

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Documento generato il 18/01/20 alle ore 13:07:20