title: Edema induction by the disintegrin-like/cysteine-rich domains from a Bothrops atrox hemorrhagin.
abstract: Viperine and crotaline snake venoms contain one or more hemorrhagic metalloproteases called hemorrhagins. The most potent hemorrhagins belong to the P-III class and have, in addition to the protease domain, disintegrin-like and cysteine-rich domains. Although proteolytic degradation of vascular endothelium basement membrane has been established to be the main factor responsible for hemorrhage, several studies reveal other factors that actually do facilitate this process. Recent evidence has shown that the nonprotease domains of the P-III class hemorrhagins are able to inhibit the platelet aggregation by blocking essential procoagulant integrins on platelets. In this study we report the identification of a hemorrhagin from Bothrops atrox venom. This enzyme, a P-III class metalloprotease, undergoes an apparent spontaneous degradation, releasing a proteic fragment containing the disintegrin-like/cysteine-rich domains. This fragment shows the capability to induce an edematogenic process, suggesting the existence of a still unknown nonenzymatic mechanism of vascular permeability increase.
authors.affiliation: Laboratório de Biologia do Reconhecer, Universidade Estadual do Norte Fluminense, Av. Alberto Lamego, 2000, Campos dos Goytacazes, Rio de Janiero, Cep 28015-620, Brazil.
authors.forename: J H
authors.initials: JH
authors.lastname: Petretski
authors.forename: M M
authors.initials: MM
authors.lastname: Kanashiro
authors.forename: F R
authors.initials: FR
authors.lastname: Rodrigues
authors.forename: E W
authors.initials: EW
authors.lastname: Alves
authors.forename: O L
authors.initials: OL
authors.lastname: Machado
authors.forename: T L
authors.initials: TL
authors.lastname: Kipnis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017837:Bothrops; D003435:Crotalid Venoms; D003545:Cysteine; D019483:Disintegrins / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced*; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010975:Platelet Aggregation Inhibitors / Q000633:toxicity*
chemical_list: D003435:Crotalid Venoms; D019483:Disintegrins; D010975:Platelet Aggregation Inhibitors; D010450:Endopeptidases; C041605:hemorrhagic proteinase IV; D003545:Cysteine