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Titolo:
CONSTITUTIVE AND PROTEIN-KINASE C-REGULATED SECRETORY CLEAVAGE OF ALZHEIMERS BETA-AMYLOID PRECURSOR PROTEIN - DIFFERENT CONTROL OF EARLY AND LATE EVENTS BY THE PROTEASOME
Autore:
MARAMBAUD P; LOPEZPEREZ E; WILK S; CHECLER F;
Indirizzi:
CNRS,INST PHARMACOL MOL & CELLULAIRE,UPR 411,660 ROUTE LUCIOLES,SOPHIA ANTIPOLIS F-06560 VALBONNE FRANCE CNRS,INST PHARMACOL MOL & CELLULAIRE,UPR 411 F-06560 VALBONNE FRANCE MT SINAI SCH MED NEW YORK NY 00000
Titolo Testata:
Journal of neurochemistry
fascicolo: 6, volume: 69, anno: 1997,
pagine: 2500 - 2505
SICI:
0022-3042(1997)69:6<2500:CAPCSC>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
MULTICATALYTIC PROTEINASE; DISEASE; PHOSPHORYLATION; APOPTOSIS; FORM; INVOLVEMENT; PEPTIDE; COMPLEX; NEURONS; BIOLOGY;
Keywords:
ALZHEIMERS DISEASE; ALPHA-SECRETASE; APP-ALPHA; PROTEASOME; LACTACYSTIN; Z-IE(OT-BU)A-LEUCINAL; PROTEIN KINASE C; HK293 CELLS; PC12 CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
P. Marambaud et al., "CONSTITUTIVE AND PROTEIN-KINASE C-REGULATED SECRETORY CLEAVAGE OF ALZHEIMERS BETA-AMYLOID PRECURSOR PROTEIN - DIFFERENT CONTROL OF EARLY AND LATE EVENTS BY THE PROTEASOME", Journal of neurochemistry, 69(6), 1997, pp. 2500-2505

Abstract

The physiological processing of the beta-amyloid precursor protein (beta APP) by a protease called alpha-secretase gives rise to APP alpha,a G-terminally truncated fragment of beta APP with known neurotrophicand cytoprotective properties. Several lines of evidence indicate that protein kinase C (PKC)-mediated events regulate this physiological pathway. We show here that the proteasome multicatalytic complex modulates the phorbol 12,13-dibutyrate-stimulated APP alpha secretion at several levels in human kidney 293 (HK293) cells. Two blocking agents of the proteasome, namely, Z-IE(Ot-Bu) A-leucinal and lactacystin, elicita dual effect on PKC-regulated APP alpha secretion by metabolically labeled HK293 cells. Thus, short periods of preincubation (2-5 h) of the cells with the inhibitors trigger a drastic potentiation of APP alpha recovery, whereas long-term treatment of the cells (15-20 h) with the blocking agents leads to an overall decrease in the secretion of APPalpha. Such a dual effect was not observed on constitutive APP alpha secretion and intracellular formation generated by HK293 cells, which both only increase upon inhibitor treatments. Similar effects on the constitutive and PKC-regulated APP alpha secretion were observed with PC12 cells. Altogether, these data suggest distinct mechanisms underlying basal and PKC-regulated APP alpha production, indicating that this multicatalytic complex appears as a key contributor of the alpha-secretase pathway.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 05:31:33