Citation

Nowatzki J, Vieira de Sene R, Paludo KS, Rizzo LE, Guimarães FD, Veiga SS, Nader HB, Franco CR, Trindade ES. Toxicon 2012; 60(3): 396-405.

Affiliation

Department of Cell Biology, Centro Politécnico, Universidade Federal do Paraná, 81531-980 Curitiba, PR, Brazil.

Copyright

(Copyright © 2012, Elsevier Publishing)

DOI

10.1016/j.toxicon.2012.04.333

PMID

22538195

Abstract

Brown spider (Loxosceles sp.) venom affects the endothelium of vessels and triggers disruptive activity in the subendothelial matrix. The vascular disorders observed after venom exposure include leukocyte and platelet activation, disseminated intravascular coagulation, an increase in vessel permeability and hemorrhage into the dermis. In this study, we report additional evidence regarding the mechanism of endothelial cell cytotoxicity induced by Loxosceles intermedia venom. Exposure to venom led to endothelial cell detachment in a time-dependent manner. Loss of cell anchorage and cell-cell adhesion following venom exposure was accompanied by changes in the distribution of the α(5)β(1) integrin and VE-cadherin. An ultrastructural analysis of cells treated with venom revealed morphological alterations characteristic of apoptosis. Moreover, after venom exposure, the ratio between Bax and Bcl-2 proteins was disturbed in favor of Bax. In addition, late apoptosis was only observed in cells detached by the action of venom. Accordingly, there was no increase in apoptosis when cells were exposed to L. intermedia venom in suspension, suggesting that the loss of cell anchorage provides the signal to initiate apoptosis. Thus, L. intermedia venom likely triggers endothelial cell death indirectly through an apoptotic mechanism known as anoikis.

Language: en