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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 is unclear...

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Autores principales: Rapôso, Catarina, Odorissi, Paulo Alexandre Miranda, Savioli, Stefania Fioravanti, Hell, Rafaela Chitarra Rodrigues, Simões, Gustavo Ferreira, Ruela-de-Sousa, Roberta R., de Oliveira, Alexandre Leite Rodrigues, da Cruz-Höfling, Maria Alice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161398/
https://www.ncbi.nlm.nih.gov/pubmed/25211468
http://dx.doi.org/10.1371/journal.pone.0107292
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author Rapôso, Catarina
Odorissi, Paulo Alexandre Miranda
Savioli, Stefania Fioravanti
Hell, Rafaela Chitarra Rodrigues
Simões, Gustavo Ferreira
Ruela-de-Sousa, Roberta R.
de Oliveira, Alexandre Leite Rodrigues
da Cruz-Höfling, Maria Alice
author_facet Rapôso, Catarina
Odorissi, Paulo Alexandre Miranda
Savioli, Stefania Fioravanti
Hell, Rafaela Chitarra Rodrigues
Simões, Gustavo Ferreira
Ruela-de-Sousa, Roberta R.
de Oliveira, Alexandre Leite Rodrigues
da Cruz-Höfling, Maria Alice
author_sort Rapôso, Catarina
collection PubMed
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.
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spelling pubmed-41613982014-09-17 Triggering of Protection Mechanism against Phoneutria nigriventer Spider Venom in the Brain Rapôso, Catarina Odorissi, Paulo Alexandre Miranda Savioli, Stefania Fioravanti Hell, Rafaela Chitarra Rodrigues Simões, Gustavo Ferreira Ruela-de-Sousa, Roberta R. de Oliveira, Alexandre Leite Rodrigues da Cruz-Höfling, Maria Alice PLoS One Research Article 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. Public Library of Science 2014-09-11 /pmc/articles/PMC4161398/ /pubmed/25211468 http://dx.doi.org/10.1371/journal.pone.0107292 Text en © 2014 Rapôso et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rapôso, Catarina
Odorissi, Paulo Alexandre Miranda
Savioli, Stefania Fioravanti
Hell, Rafaela Chitarra Rodrigues
Simões, Gustavo Ferreira
Ruela-de-Sousa, Roberta R.
de Oliveira, Alexandre Leite Rodrigues
da Cruz-Höfling, Maria Alice
Triggering of Protection Mechanism against Phoneutria nigriventer Spider Venom in the Brain
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161398/
https://www.ncbi.nlm.nih.gov/pubmed/25211468
http://dx.doi.org/10.1371/journal.pone.0107292
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