| Full text | |
| Author(s): |
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]
Total Authors: 6
|
| Affiliation: | [1] Inst Butantan, CAT Cepid, Lab Especial Toxinol Aplicada, BR-05503900 Sao Paulo - Brazil
[2] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 - USA
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | THROMBOSIS AND HAEMOSTASIS; v. 104, n. 3, p. 485-497, SEP 2010. |
| Web of Science Citations: | 36 |
| Abstract | |
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) | |
| FAPESP's process: | 98/14307-9 - Center for Applied Toxinology |
| Grantee: | Hugo Aguirre Armelin |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |