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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Triggering of Protection Mechanism against Phoneutria nigriventer Spider Venom in the Brain

Texto completo
Autor(es):
Raposo, Catarina [1] ; Miranda Odorissi, Paulo Alexandre [1] ; Savioli, Stefania Fioravanti [1] ; Rodrigues Hell, Rafaela Chitarra [2] ; Simoes, Gustavo Ferreira [2] ; Ruela-de-Sousa, Roberta R. [1] ; Rodrigues de Oliveira, Alexandre Leite [2] ; da Cruz-Hoefling, Maria Alice [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, UNICAMP, Dept Biochem & Tissue Biol, Sao Paulo - Brazil
[2] Univ Estadual Campinas, UNICAMP, Dept Funct & Struct Biol, Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 9, n. 9 SEP 11 2014.
Citações Web of Science: 11
Resumo

Severe accidents caused by the ``armed'' spider Phoneutria nigriventer cause neurotoxic manifestations in victims. In experiments with rats, P. nigriventer venom (PNV) temporarily disrupts the properties of the BBB by affecting both the transcellular and the paracellular route. However, it is unclear how cells and/or proteins participate in the transient opening of the BBB. The present study demonstrates that PNV is a substrate for the multidrug resistance protein-1 (MRP1) in cultured astrocyte and endothelial cells (HUVEC) and increases mrp1 and cx43 and down-regulates glut1 mRNA transcripts in cultured astrocytes. The inhibition of nNOS by 7-nitroindazole suggests that NO derived from nNOS mediates some of these effects by either accentuating or opposing the effects of PNV. In vivo, MRP1, GLUT1 and Cx43 protein expression is increased differentially in the hippocampus and cerebellum, indicating region-related modulation of effects. PNV contains a plethora of Ca2+, K+ and Na+ channel-acting neurotoxins that interfere with glutamate handling. It is suggested that the findings of the present study are the result of a complex interaction of signaling pathways, one of which is the NO, which regulates BBB-associated proteins in response to PNV interference on ions physiology. The present study provides additional insight into PNV-induced BBB dysfunction and shows that a protective mechanism is activated against the venom. The data shows that PNV has qualities for potential use in drug permeability studies across the BBB. (AU)

Processo FAPESP: 07/50272-6 - Veneno e toxina de aranha phoneutria nigriventer: acao no sistema nervoso central.
Beneficiário:Catarina Raposo Dias Carneiro
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 07/56715-7 - Expressão do transportador de glicose (GLUT-1), da conexina 43 (Cx-043) e da proteína associada à multirresistência (MRP-4) na intoxicação pelo veneno bruto da aranha Phoneutria nigriventer em ratos
Beneficiário:Paulo Alexandre Miranda Odorissi
Modalidade de apoio: Bolsas no Brasil - Iniciação Científica