title: Brown spider (Loxosceles intermedia) venom triggers endothelial cells death by anoikis.
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 α₅β₁ 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.
authors.affiliation: Department of Cell Biology, Federal University of Paraná, 81351-980, Curitiba, PR, Brazil.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Nowatzki
authors.forename: Reginaldo Vieira
authors.initials: RV
authors.lastname: Sene
authors.forename: Katia Sabrina
authors.initials: KS
authors.lastname: Paludo
authors.forename: Luiz Eduardo
authors.initials: LE
authors.lastname: Rizzo
authors.forename: Fernando
authors.initials: F
authors.lastname: Souza-Fonseca-Guimarães
authors.forename: Silvio Sanches
authors.initials: SS
authors.lastname: Veiga
authors.forename: Helena Bonciani
authors.initials: HB
authors.lastname: Nader
authors.forename: Célia Regina C
authors.initials: CR
authors.lastname: Franco
authors.forename: Edvaldo S
authors.initials: ES
authors.lastname: Trindade
mesh_terms: D000818:Animals; D023102:Anoikis / Q000187:drug effects*; D015703:Antigens, CD / Q000378:metabolism; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001938:Brazil; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D039081:Integrin alpha5beta1 / Q000378:metabolism; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D011817:Rabbits; D013111:Spider Venoms / Q000494:pharmacology*; D013112:Spiders / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D015820:Cadherins; D039081:Integrin alpha5beta1; D013111:Spider Venoms; D000099152:Cadherin 5