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Master's Dissertation
DOI
10.11606/D.42.2009.tde-27012010-095359
Document
Author
Full name
Mara Adriana Corrêa
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Tambourgi, Denise Vilarinho (President)
Cury, Yara
Farsky, Sandra Helena Poliselli
Title in Portuguese
Mecanismos de ação de metaloproteases endógenas na injúria de queratinócitos humanos induzida pelo veneno de Loxosceles laeta e a SMase I.
Keywords in Portuguese
Loxosceles laeta
Aracnídeos
Aranhas
Células epiteliais
Lipídeos
Metaloproteinases
Veneno de origem animal
Abstract in Portuguese
O envenenamento por aranhas Loxosceles é caracterizado pelo desenvolvimento de dermonecrose. A expressão de metaloproteases induzidas pelas esfingomielinases do veneno pode estar envolvida no loxoscelismo cutâneo. Os resultados mostraram que o veneno de Loxosceles laeta e a proteína recombinante SMase I foram capazes de: induzir a expressão de metaloproteases (MMP-2, MMP-7 e MMP-9); diminuir a expressão de alguns marcadores de superfície e causar morte celular. A indução de MMP-7, como produto da ação do veneno e da SMase I de L. laeta, não foi reportada em outras espécies do gênero. O uso de inibidores de metaloproteases, como a tetraciclina, impediu a morte celular e reduziu a expressão de MMPs. A galardina, um composto que inibe metaloproteases da família das adamlisinas e das MMPs, evitou a clivagem dos marcadores MCP, 2-microglobulina, MHCI, EPCR em queratinócitos humanos tratados. Os resultados revelam que a inibição das metaloproteases de matriz extracelular e da família das adamlisinas pode ser uma alternativa eficaz no tratamento do loxoscelismo cutâneo.
Title in English
Action mechanisms of endogenous metalloproteinases in human keratinocytes injury induced by Loxosceles laeta spider venom and SMase I.
Keywords in English
Loxosceles laeta
Arachnids
Epithelial cells
Lipids
Metalloproteinases
Poison of animal origin
Spiders
Abstract in English
The envenomation by Loxosceles spider characterized by the development of dermonecrosis. Metalloproteinases expression, induced by venom sphingomyelinases, may be involved in cutaneous loxoscelism. The results showed that Loxosceles laeta venom and the recombinant protein SMase I were able to: induce the expression of matrix metalloproteinases (MMP-2, MMP-7 e MMP-9); reduce the expression of some surface markers and cause cell death. The induction of MMP-7, as a product of venom and SMase I action, has not been reported for other genus species. The use of metalloproteinase inhibitors, such as tetracycline, prevented cell death and reduced MMPs expression. Galardin, a compound that inhibits metalloproteinases from the adamlisins family and MMPs, avoided the cleavage of MCP, 2-microglobulin, MHCI and EPCR on the surface of the treated human keratinocytes. These data indicate that inhibition of metalloproteinases can be an effective alternative on the cutaneous loxoscelism treatment.
 
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Publishing Date
2010-02-25
 
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