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Titolo:
INHIBITION OF COLLAGEN-INDUCED PLATELET-AGGREGATION AS THE RESULT OF CLEAVAGE OF ALPHA(2)BETA(1)-INTEGRIN BY THE SNAKE-VENOM METALLOPROTEINASE JARARHAGIN
Autore:
KAMIGUTI AS; HAY CRM; ZUZEL M;
Indirizzi:
UNIV LIVERPOOL,ROYAL LIVERPOOL HOSP,DEPT HAEMATOL LIVERPOOL L69 3BX MERSEYSIDE ENGLAND
Titolo Testata:
Biochemical journal
, volume: 320, anno: 1996,
parte:, 2
pagine: 635 - 641
SICI:
0264-6021(1996)320:<635:IOCPAT>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
BOTHROPS-JARARACA VENOM; HEMORRHAGIC METALLOPROTEINASES; BLOOD-PLATELETS; VIPER VENOMS; I-DOMAIN; INTEGRIN; GLYCOPROTEIN; RECEPTOR; PROTEIN; ALPHA-2-MACROGLOBULIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
A.S. Kamiguti et al., "INHIBITION OF COLLAGEN-INDUCED PLATELET-AGGREGATION AS THE RESULT OF CLEAVAGE OF ALPHA(2)BETA(1)-INTEGRIN BY THE SNAKE-VENOM METALLOPROTEINASE JARARHAGIN", Biochemical journal, 320, 1996, pp. 635-641

Abstract

Jararhagin is a high-molecular-mass (52 kDa) haemorrhagic metalloproteinase from Bothrops jararaca venom and a member of the metalloproteinase/disintegrin/cysterin-rich protein family. The disintegrin domain of jararhagin has been implicated in the inhibition of platelet responses to collagen by a mechanism that is not entirely known. The present investigation demonstrates that both active and 1,10-phenanthroline-inactivated jararhagin inhibit platelet aggregation by collagen with an IC50 of 40 and 140 nM respectively. The apparently higher inhibitory effect of the active enzyme clearly indicates that, in addition to the disintegrin region, the metalloproteinase domain of jararhagin also participates in this inhibition. As collagen interacts with platelets via alpha(2) beta(1)-integrin, we investigated the effects of jararhaginon this integrin using selected function-blocking monoclonal antibodies against both of its subunits. Flow cytometry of platelets treated with native jararhagin and immunoprecipitation of platelet surface glycoproteins from lysates after jararhagin treatment showed an apparentlyselective reduction of alpha(2) beta(1)- integrin immunoreactivity with both anti-alpha(2) and anti-beta(1) monoclonal antibodies. The lossof immunoreactivity was not due to integrin internalization, since italso took place in cytochalasin D-treated platelets. Here we show that jararhagin cleaved isolated alpha(2) beta(1)-integrin resulting in the generation of a 115 kDa beta(1) fragment. We therefore propose thatthe inhibition by jararhagin of platelet response to collagen is mediated through the binding of jararhagin to platelet alpha(2)-subunit via the disintegrin domain, followed by proteolysis of the beta(1)-subunit with loss of the integrin structure (conformation) necessary for the binding of macromolecular ligands.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 06:09:12