The snake venom metalloproteases berythractivase and jararhagin activate endothelial cells.
PIII snake venom metalloproteases (SVMPs) are metalloproteases structurally related to ADAMs (a disintegrin and metalloprotease human family of proteins). Berythractivase and jararhagin are PIII SVMPs with 69% homology that have different hemostatic properties. In order to clarify these differences and further characterize the biological effects of these proteins, we have analyzed the effect of both proteases on human umbilical-vein endothelial cell functions. We found that both proteins enhanced nitric oxide generation, prostacyclin production and interleukin-8 release. Berythractivase but not jararhagin increased the expression of decay accelerating factor. Jararhagin decreased cell viability in a concentration-dependent manner and induced cellular apoptosis, while berythractivase did not modulate cell survival. Our results show for the first time that, besides the known anti-aggregating or procoagulant effects of PIII SVMPs, these proteins trigger endothelial cell effector responses. Although structurally related, berythractivase and jararhagin induce a dissimilar generation and release of endothelial molecules that may account for their different hemorrhagic activity.
Schattner
Mirta
M
Department of Thrombosis and Hemostasis, National Academy of Medicine, National Research Council (CONICET), 1425 Buenos Aires, Argentina.
Fritzen
Márcio
M
Ventura
Janaína de Souza
Jde S
de Albuquerque Modesto
Jeanne Claíne
JC
Pozner
Roberto Gabriel
RG
Moura-da-Silva
Ana Maria
AM
Chudzinski-Tavassi
Ana Marisa
AM
D000818:Animals; D017837:Bothrops; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003435:Crotalid Venoms / Q000737:chemistry / Q000201:enzymology* / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology*; D000097146:Bothrops jararaca Venom
D003435:Crotalid Venoms; D008666:Metalloendopeptidases; D000097146:Bothrops jararaca Venom; C504090:berythractivase, Bothrops erythromelas