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Titolo:
The caspase-derived C-terminal fragment of beta APP induces caspase-independent toxicity and triggers selective increase of A beta 42 in mammalian cells
Autore:
Dumanchin-Njock, C; da Costa, CA; Mercken, L; Pradier, L; Checler, F;
Indirizzi:
Univ Nice Sophia Antipolis, CNRS, UMR6097, IPMC, F-06560 Valbonne, France Univ Nice Sophia Antipolis Valbonne France F-06560 6560 Valbonne, France Aventis Pharma, Vitry Sur Seine, France Aventis Pharma Vitry Sur Seine France s Pharma, Vitry Sur Seine, France
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 5, volume: 78, anno: 2001,
pagine: 1153 - 1161
SICI:
0022-3042(200109)78:5<1153:TCCFOB>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; CYTOPLASMIC DOMAIN; WILD-TYPE; APOPTOSIS; SECRETION; PEPTIDE; PROTEASES; BINDING; PRESENILIN-1;
Keywords:
Alzheimer's disease; amyloid; beta-amyloid precursor protein; caspases; HEK293 cells TSM1 neurons;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Checler, F Univ Nice Sophia Antipolis, CNRS, UMR6097, IPMC, 660 Route Lucioles, F-06560 Valbonne, France Univ Nice Sophia Antipolis 660 Route Lucioles Valbonne France F-06560
Citazione:
C. Dumanchin-Njock et al., "The caspase-derived C-terminal fragment of beta APP induces caspase-independent toxicity and triggers selective increase of A beta 42 in mammalian cells", J NEUROCHEM, 78(5), 2001, pp. 1153-1161

Abstract

During its physiopathological maturation, the p-amyloid precursor protein undergoes several distinct proteolytic events by activities called secretases. In Alzheimer's disease, the main histological hallmark called senile plaque is clearly linked to the overproduction of the amyloid peptides A beta40 and A beta 42, two highly aggregable beta APP-derived fragments generated by combined cleavages by beta- and gamma -secretases. Recently, an alternative hydrolytic pathway was described, involving another category of proteolytic activities called caspases, responsible for the production of a 31 amino acids beta APP C-terminal fragment called C31. C31 was reported to lower the viability of N2a cells but the exact mechanisms mediating C31-toxicity remained to be established. Here we show that the transient transfection of pSV2 vector encoding C31 lowers by about 80% TSM1 neuronal cells viability. Arguing against a C31-stimulated apoptotic response, we demonstrate by combined enzymatic and immunological approaches that C31 expression did not modulate basal or staurosporine-induced caspase 3-like activity and pro-caspase-3 activation. Furthermore, C31 did not modify Bax and p53 expressions, poly-(ADP-ribose)-polymerase cleavage and cytochrome c translocation into the cytosol. However, we established that C31 overexpression triggers selective increase of A beta 42 but not A beta 40 production by HEK293 cells expressing wild-type beta APP751. Altogether, our data demonstrate that C31induces a caspase-independent toxicity in TSM1 neurons and potentiates thepathogenic beta APP maturation pathway by increasing selectively A beta 42species in wild type-beta APP-expressing human cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 08:28:00