New insights into the structural elements involved in the skin haemorrhage induced by snake venom metalloproteinases

Autor(es)

Oliveira, Ana K. ^[1] ; Leme, Adriana F. Paes ^[1] ; Asega, Amanda F. ^[1] ; Camargo, Antonio C. M. ^[1] ; Fox, Jay W. ^[2] ; Serrano, Solange M. T. ^[1]

Afiliação do(s) autor(es)

^[1] Inst Butantan, CAT Cepid, Lab Especial Toxinol Aplicada, BR-05503900 Sao Paulo - Brazil

^[2] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 - USA

• Tipo de documento: Artigo Científico
• Fonte: THROMBOSIS AND HAEMOSTASIS; v. 104, n. 3, p. 485-497, SEP 2010.
• Citações Web of Science: 36

Resumo

Haemorrhage induced by snake venom metalloproteinases (SVMPs) is a complex phenomenon resulting in capillary disruption and extravasation. This study analysed structural elements important for the interaction of four Bothrops jararaca SVMPs of different domain organisation and glycosylation levels with plasma and extracellular matrix proteins: HF3 (P-III class) is highly glycosylated and similar to 80 times more haemorrhagic than bothropasin (P-III class), which has a minor carbohydrate moiety; BJ-PI (P-I class) is not haemorrhagic and the DC protein is composed of disintegrin-like/cysteine-rich domains of bothropasin. HF3, bothropasin and BJ-PI showed different degradation profiles of fibrinogen, fibronectin, vitronectin, von Willebrand factor, collagens IV and VI, laminin and Matrigel (TM); however, only bothropasin degraded collagen I. In solid-phase binding assays HF3 and bothropasin interacted with fibrinogen, fibronectin, laminin, collagens I and VI; the DC protein bound only to collagens I and VI; however, no binding of BJ-PI to these proteins was detected. N-deglycosylation caused loss of structural stability of bothropasin and BJ-PI but HF3 remained intact, although its haemorrhagic and fibrinogenolytic activities were partially impaired. Nevertheless, N-deglycosylated HF3 bound with higher affinity to collagens I and VI, although its proteolytic activity upon these collagens was not enhanced. This study demonstrates that features of carbohydrate moieties of haemorrhagic SVMPs may play a role in their interaction with substrates of the extracellular matrix, and the ability of SVMPs to degrade proteins in vitro does not correlate to their ability to cause haemorrhage, suggesting that novel, systemic approaches are necessary for understanding the mechanism of haemorrhage generation by SVMPs. (AU)

• Processo FAPESP: 98/14307-9 - Center for Applied Toxinology
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 04/15974-1 - Estudo sobre a função do domínio rico em cisteínas do fator hemorrágico 3 (HF3), metaloproteinases do veneno da serpente Bothrops jararaca, na interação com seus alvos celulares e plasmáticos
• Beneficiário: Solange Maria de Toledo Serrano
• Modalidade de apoio: Auxílio à Pesquisa - Regular