eNOS uncoupling in the cerebellum after BBB disruption by exposure to Phoneutria nigriventer spider venom

Autor(es)

Soares, Edilene Siqueira ^[1] ; Padilha Mendonca, Monique Culturato ^{[1, 2]} ; da Cruz-Hoefling, Maria Alice ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, BR-13083970 Campinas, SP - Brazil

^[2] State Univ Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 104, p. 7-13, SEP 15 2015.
• Citações Web of Science: 7

Resumo

Numerous studies have shown that the venom of Phoneutria nigriventer (PNV) armed-spider causes excitotoxic signals and blood-brain barrier breakdown (BBBb) in rats. Nitric oxide (NO) is a signaling molecule which has a role in endothelium homeostasis and vascular health. The present study investigated the relevance of endothelial NO synthase (eNOS) uncoupling to clinical neurotoxic evolution induced by PNV. eNOS immunoblotting of cerebellum lysates processed through low-temperature SDS-PAGE revealed significant increased monomerization of the enzyme at critical periods of severe envenoming (1-2 h), whereas eNOS dimerization reversal paralleled to amelioration of animals condition (5-72 h). Moreover, eNOS uncoupling was accompanied by increased expression in calcium-sensing calmodulin protein and calcium-binding calbindin-D28 protein in cerebellar neurons. It is known that greater eNOS monomers than dimers implies the inability of eNOS to produce NO leading to superoxide production and endothelial/vascular barrier dysfunction. We suggest that transient eNOS deactivation and disturbances in calcium handling reduce NO production and enhance production of free radicals thus contributing to endothelial dysfunction in the cerebellum of envenomed rats. In addition, eNOS uncoupling compromises the enzyme capacity to respond to shear stress contributing to perivascular edema and it is one of the mechanisms involved in the BBBb promoted by PNV. (C) 2015 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 05/53625-1 - Ação dos mastoparanos e da fosfolipase A2 isolados do veneno de Polybia paulista (Hymenoptera, Epiponini) nos mecanismos de apoptose e necrose de células musculares e mitocôndrias isoladas de camundongos Balb/c
• Beneficiário: Maria Alice da Cruz Hofling
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/24782-5 - Óxido de grafeno e sistema nervoso central: avaliação dos efeitos na barreira hematoencefálica e perfil nanotoxicológico
• Beneficiário: Monique Culturato Padilha Mendonça
• Modalidade de apoio: Bolsas no Brasil - Doutorado