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Titolo:
Short- and long-term effect of acetylcholinesterase inhibition on the expression and metabolism of the amyloid precursor protein
Autore:
Racchi, M; Sironi, M; Caprera, A; Konig, G; Govoni, S;
Indirizzi:
Univ Pavia, Dept Expt & Appl Pharmacol, I-27100 Pavia, Italy Univ Pavia Pavia Italy I-27100 pt & Appl Pharmacol, I-27100 Pavia, Italy Bayer AG, Pharma Res CNS, D-5600 Wuppertal, Germany Bayer AG Wuppertal Germany D-5600 rma Res CNS, D-5600 Wuppertal, Germany
Titolo Testata:
MOLECULAR PSYCHIATRY
fascicolo: 5, volume: 6, anno: 2001,
pagine: 520 - 528
SICI:
1359-4184(200109)6:5<520:SALEOA>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALZHEIMERS-DISEASE; BETA-PROTEIN; NEUROBLASTOMA-CELLS; RAT-BRAIN; SECRETION; METRIFONATE; FIBROBLASTS; ACTIVATION; CLEAVAGE; RECEPTOR;
Keywords:
amyloid precursor protein; cholinergic transmission; acetylcholinesterase inhibitors; neuroblastoma cell lines; protein kinase C;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Racchi, M Univ Pavia, Dept Expt & Appl Pharmacol, Viale Taramelli 14, I-27100 Pavia,Italy Univ Pavia Viale Taramelli 14 Pavia Italy I-27100 0 Pavia,Italy
Citazione:
M. Racchi et al., "Short- and long-term effect of acetylcholinesterase inhibition on the expression and metabolism of the amyloid precursor protein", MOL PSYCHI, 6(5), 2001, pp. 520-528

Abstract

We have investigated the acute and chronic effect of metrifonate (MTF) anddichlorvos (DDVP), respectively the prodrug and active acetylcholinesterase inhibitor, on the secretory processing of the amyloid precursor protein (APP) in SH-SY5Y neuroblastoma cells. We demonstrate that the acute treatment of SH-SY5Y cells with both compounds results in an increased secretion ofthe soluble fragment of APP (sAPP alpha) into the conditioned media of cells, with a pattern correlated to the level of acetycholinesterase inhibition. The regulation of APP processing in these conditions is mediated by an indirect cholinergic effect on muscarinic receptors, as demonstrated by inhibition with atropine. We have also followed APP expression and metabolism after long-term treatment with metrifonate. Treated cells showed reduced AChE activity after 24, 48 h and also following 7 days of repeated treatment, a time point at which increased AChE expression was detectable. At all timepoints sAPP alpha release was unaffected suggesting that enhanced sAPP alpha release by MTF is transitory, nevertheless the sensitivity of cholinergic receptors was unchanged, as indicated by the fact that cholinergic response can be elicited similarly in untreated and treated cells. APP gene expression was unaffected by long-term AChE inhibition suggesting that increasedshort-term sAPP alpha release does not elicit compensatory effects.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/20 alle ore 21:08:53