Triggering of protection mechanism against Phoneutria nigriventer spider venom in the brain.

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 i...

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Autores principales:	Catarina Rapôso, Paulo Alexandre Miranda Odorissi, Stefania Fioravanti Savioli, Rafaela Chitarra Rodrigues Hell, Gustavo Ferreira Simões, Roberta R Ruela-de-Sousa, Alexandre Leite Rodrigues de Oliveira, Maria Alice da Cruz-Höfling
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b102015418364a4db3a6d7ad3ff767f4
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spelling	oai:doaj.org-article:b102015418364a4db3a6d7ad3ff767f42021-11-25T06:00:55ZTriggering of protection mechanism against Phoneutria nigriventer spider venom in the brain.1932-620310.1371/journal.pone.0107292https://doaj.org/article/b102015418364a4db3a6d7ad3ff767f42014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107292https://doaj.org/toc/1932-6203Severe 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 Ca(2+), 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.Catarina RapôsoPaulo Alexandre Miranda OdorissiStefania Fioravanti SavioliRafaela Chitarra Rodrigues HellGustavo Ferreira SimõesRoberta R Ruela-de-SousaAlexandre Leite Rodrigues de OliveiraMaria Alice da Cruz-HöflingPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107292 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Catarina Rapôso Paulo Alexandre Miranda Odorissi Stefania Fioravanti Savioli Rafaela Chitarra Rodrigues Hell Gustavo Ferreira Simões Roberta R Ruela-de-Sousa Alexandre Leite Rodrigues de Oliveira Maria Alice da Cruz-Höfling Triggering of protection mechanism against Phoneutria nigriventer spider venom in the brain.
description	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 Ca(2+), 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.
format	article
author	Catarina Rapôso Paulo Alexandre Miranda Odorissi Stefania Fioravanti Savioli Rafaela Chitarra Rodrigues Hell Gustavo Ferreira Simões Roberta R Ruela-de-Sousa Alexandre Leite Rodrigues de Oliveira Maria Alice da Cruz-Höfling
author_facet	Catarina Rapôso Paulo Alexandre Miranda Odorissi Stefania Fioravanti Savioli Rafaela Chitarra Rodrigues Hell Gustavo Ferreira Simões Roberta R Ruela-de-Sousa Alexandre Leite Rodrigues de Oliveira Maria Alice da Cruz-Höfling
author_sort	Catarina Rapôso
title	Triggering of protection mechanism against Phoneutria nigriventer spider venom in the brain.
title_short	Triggering of protection mechanism against Phoneutria nigriventer spider venom in the brain.
title_full	Triggering of protection mechanism against Phoneutria nigriventer spider venom in the brain.
title_fullStr	Triggering of protection mechanism against Phoneutria nigriventer spider venom in the brain.
title_full_unstemmed	Triggering of protection mechanism against Phoneutria nigriventer spider venom in the brain.
title_sort	triggering of protection mechanism against phoneutria nigriventer spider venom in the brain.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/b102015418364a4db3a6d7ad3ff767f4
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Triggering of protection mechanism against Phoneutria nigriventer spider venom in the brain.

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