Hemorrhagic Activity of HF3, a Snake Venom Metalloproteinase: Insights from the Proteomic Analysis of Mouse Skin and Blood Plasma

Autor(es)

Paes Leme, Adriana F. ^{[1, 2]} ; Sherman, Nicholas E. ^[3] ; Smalley, David M. ^[3] ; Sizukusa, Leticia O. ^[2] ; Oliveira, Ana K. ^[2] ; Menezes, Milene C. ^[2] ; Fox, Jay W. ^[3] ; Serrano, Solange M. T. ^[2]

Afiliação do(s) autor(es)

^[1] Lab Nacl Biociencias LNBio, Campinas, SP - Brazil

^[2] Inst Butantan, Lab Especial Toxinol Aplicada, CAT Cepid, BR-05503900 Sao Paulo - Brazil

^[3] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PROTEOME RESEARCH; v. 11, n. 1, p. 279-291, JAN 2012.
• Citações Web of Science: 31

Resumo

Hemorrhage induced by snake venom metalloprotellases (SVMPs) is a complex phenomenon resulting in capillary disruption and blood extravasation. The mechanism of action of SVMPs has been investigated using various methodologies however the precise molecular events associated with microvessel disruption remains not fully understood. To gain insight into the hemorrhagic process, we analyzed the global effects of HF3, an extremely hemorrhagic SVMP from Bothrops jararaca, in the mouse skin and plasma. We report that in the HF3-treated skin there was evidence of degradation of extracellular matrix (collagens and proteoglycans), cytosolic, cytoskeleton, and plasma proteins. Furthermore, the data suggest that direct and indirect effects promoted by HF3 contributed to tissue injury as the activation of collagenases was detected in the HF3-treated skin. In the plasma analysis after depletion of the 20 most abundant proteins, fibronectin appeared as degraded by HF3. In contrast, some plasma proteinase inhibitors showed higher abundance compared to control skin and plasma. This is the first study to assess the complex in vivo effects of HF3 using high-throughput protcomic approaches, and the results underscore a scenario characterized by the interplay between the hydrolysis of intracellular, extracellular, and plasma proteins and the increase of plasma inhibitors in the hemorrhagic process. (AU)

• Processo FAPESP: 04/14846-0 - Rede de proteoma do estado de São Paulo
• Beneficiário: Fabio Cesar Gozzo
• Modalidade de apoio: Auxílio à Pesquisa - Programa GENOMA
• Processo FAPESP: 06/50059-8 - Proteômica aplicada ao estudo dos alvos celulares e plasmáticos do HF3, uma metaloproteinase do veneno da serpente Bothrops jararaca com atividades hemorrágica e inflamatória
• Beneficiário: Adriana Franco Paes Leme
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• 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