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Doctoral Thesis
DOI
10.11606/T.87.2019.tde-30012019-163207
Document
Author
Full name
Cristiani Baldo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Silva, Ana Maria Moura da (President)
Coelho, Thereza Christina Barja Fidalgo
Serrano, Solange Maria de Toledo
Tavassi, Ana Marisa Chudzinski
Zorn, Telma Maria Tenorio
Title in Portuguese
Mecanismos envolvidos na ação hemorrágica de metaloproteinases de venenos de serpentes.
Keywords in Portuguese
Colágeno
Hemorragia
Jararagina
Metaloproteinases
Veneno de serpentes
Abstract in Portuguese
Com o objetivo de estudar as diferenças de potencial hemorrágico entre metaloproteinases de venenos de serpentes (SVMPs), compararamos a ação da jararagina, toxina hemorrágica da classe P-III, e da BnP1, SVMP da classe P-I fracamente hemorrágica, quanto à ação em proteínas de matriz extracelular (MEC), células endoteliais e distribuição na MEC e endotélio. Nos ensaios de ligação em fase sólida, apenas a jararagina e a jarararagina-C (domínios tipo disintegrina e rico em cisteínas) se ligaram ao colágeno I e IV. Em HUVECs, a jararagina e BnP1 induziram apoptose, mas em modelo de pele, apenas a jararagina induziu intensa hemorragia, acompanhada de degradação do colágeno fibrilar e colágeno IV na região da hipoderme. A jararagina e jararagina-C localizaram-se na parede dos capilares sangüíneos co-localizando-se como o colágeno IV. Esses resultados sugerem que a ligação ao colágeno é importante para a hemorragia induzida pelas SVMPs da classe P-III, promovendo seu acúmulo nas proximidades dos vasos sanguíneos tornando a catalise dos componentes da MEC mais eficiente.
Title in English
Mechanisms involved in the hemorrhage induced by snake venom metalloproteinases.
Keywords in English
Collagen
Hemorrhage
Jararhagin
Metalloproteinases
Snake venom
Abstract in English
In order to enlighten the mechanisms of hemorrhage induced by snake venom metalloproteinases (SVMPs), the effects of jararhagin, a highly hemorrhagic P-III SVMP and BnP1, a weakly hemorrhagic P-I SVMP, on extracellular matrix (ECM) proteins, endothelial cells, and distribution in MEC and endothelium, was compared. In solid phase assay, only jararhagin and jararhagin-C (disintegrin-like and cysteine-rich domains) bond to collagen I and IV. In HUVECs, jararhagin and BnP1 induced apoptosis, but in skin model only jararhagin induced intense hemorrhage with degradation of the fibrillar collagen and collagen I, in hypodermis region. Jararhagin and jararhagin-C concentrated in blood vessels walls, co-localizing with collagen IV. These results suggest that the collagen binding is important to hemorrhage induced by P-III SVMPs, promoting their accumulation near to the blood vessels, making the catalysis of the basement membrane components more efficient.
 
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Publishing Date
2019-01-30
 
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