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Titolo:
Ca2+ influx and cAMP elevation overcame botulinum toxin A but not tetanus toxin inhibition of insulin exocytosis
Autore:
Huang, XH; Kang, YH; Pasyk, EA; Sheu, L; Wheeler, MB; Trimble, WS; Salapatek, A; Gaisano, HY;
Indirizzi:
Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 t Med, Toronto, ON M5S 1A8, Canada Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 ysiol, Toronto, ON M5S 1A8, Canada Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 ochem, Toronto, ON M5S 1A8, Canada Hosp Sick Children, Res Inst, Cell Biol Program, Toronto, ON M5G 1X8, Canada Hosp Sick Children Toronto ON Canada M5G 1X8 Toronto, ON M5G 1X8, Canada
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
fascicolo: 3, volume: 281, anno: 2001,
pagine: C740 - C750
SICI:
0363-6143(200109)281:3<C740:CIACEO>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
SYNAPTOSOME-ASSOCIATED PROTEIN; LIGHT-CHAIN; NEUROTRANSMITTER RELEASE; CLOSTRIDIAL NEUROTOXINS; KINETIC COMPONENTS; PANCREATIC-ISLETS; CHROMAFFIN CELLS; MEMBRANE-FUSION; ACINAR-CELLS; BETA-CELLS;
Keywords:
vesicle-associated membrane protein-2; synaptosomal-associated protein of 25 kilodaltons; clostridial neurotoxins; insulin exocytosis; capacitance measurements; adenosine 3 ',5 '-cyclic monophosphate;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Gaisano, HY Univ Toronto, Dept Med, Rm 7226,Med Sci Bldg, Toronto, ON M5S 1A8, Canada Univ Toronto Rm 7226,Med Sci Bldg Toronto ON Canada M5S 1A8 da
Citazione:
X.H. Huang et al., "Ca2+ influx and cAMP elevation overcame botulinum toxin A but not tetanus toxin inhibition of insulin exocytosis", AM J P-CELL, 281(3), 2001, pp. C740-C750

Abstract

Previous reports showed that cleavage of vesicle-associated membrane protein-2 (VAMP-2) and synaptosomal-associated protein of 25 kDa (SNAP-25) by clostridial neurotoxins in permeabilized insulin-secreting p-cells inhibited Ca2+-evoked insulin secretion. In these reports, the soluble N-ethylmaleimide-sensitive factor attachment protein target receptor proteins might have formed complexes, which preclude full accessibility of the putative sites for neurotoxin cleavage. In this work, VAMP-2 and SNAP-25 were effectively cleaved before they formed toxin-insensitive complexes by transient transfection of insulinoma HIT or INS-1 cells with tetanus toxin (TeTx) or botulinum neurotoxin A (BoNT/A), as shown by immunoblotting and immunofluorescence microscopy. This resulted in an inhibition of Ca2+ (glucose or KCl)-evoked insulin release proportionate to the transfection efficiency (40-50%) and an accumulation of insulin granules. With the use of patch-clamp capacitancemeasurements, Ca2+-evoked exocytosis by membrane depolarization to -10 mV was abolished by TeTx (6% of control) but only moderately inhibited by BoNT/A (30% of control). Depolarization to 0 mV to maximize Ca2+ influx partially overcame BoNT/A (60% of control) but not TeTx inhibition. Of note, cAMP activation potentiated Ca2+-evoked secretion by 129% in control cells but only 55% in BoNT/A-transfected cells and had negligible effects in TeTx-transfected cells. These results indicate that, whereas VAMP-2 is absolutely necessary for insulin exocytosis, the effects of SNAP-25 depletion on exocytosis, perhaps on insulin granule pool priming or mobilization steps, could be partially reversed by higher levels of Ca2+ or cAMP potentiation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 11:14:05