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Type: Artigo de periódico
Title: Effect of Phoneutria nigriventer Venom on the Expression of Junctional Protein and P-gp Efflux Pump Function in the Blood-Brain Barrier
Author: Raposo, C
Odorissi, PAM
Oliveira, ALR
Aoyama, H
Ferreira, CV
Verinaud, L
Fontana, K
Ruela-de-Sousa, RR
da Cruz-Hofling, MA
Abstract: Phoneutria nigriventer spider venom (PNV) contains Ca2+, K+ and Na+ channel-acting peptides that affect neurotransmitter release and causes excitotoxicity in PNS and CNS. It has been demonstrated that PNV causes blood-brain barrier (BBB) breakdown of hippocampal microvessels time-dependently through enhanced microtubule-mediated vesicular transport. Herein, it is hypothesized that PNV can cause BBB breakdown in the hippocampus and cerebellum time-dependently through other molecular mechanisms. The BBB integrity was assessed through the analysis of expression of Poly-glycoprotein (P-gp) efflux transporter protein, laminin from basement membrane and endothelial tight junctional and adhesion junctional (TJ/AJ) proteins. Phosphatase and tensin homolog (PTEN) and protein phosphatase 2A (PP2A) expression, which are known to have a role in the phosphorylation of junctional proteins and BBB opening, were also investigated. Astrocytes P-gp activity was determined by flow cytometry. The study demonstrated temporary decreased expression of laminin, TJ and AJ proteins (ZO1//occludin//claudin-5//beta-catenin) and P-gp (more prominently in hippocampus), which was completely or partially resolved between 2 and 5 h (and more quickly for cerebellum). PNV inhibited P-gp activity in astrocytes. PP2A phosphorylation, which inhibits the enzyme activity, was increased in both regions (15-45 min); however the phosphorylation level returned to baseline after 2 h. In conclusion, PNV disrupts paracellular transport in the BBB and possesses substrates for the active P-gp efflux transporter located in the BBB complex. Further studies into cellular mechanisms of astrocyte/endothelial interactions, using PNV as tool, may identify how astrocytes regulate the BBB, a characteristic that may be useful for the temporary opening of the BBB.
Subject: Astrocytes
Blood-brain barrier
Endothelial cells
Tight and adhesion proteins
Efflux protein
Basement membrane
Spider venom
Country: EUA
Editor: Springer/plenum Publishers
Citation: Neurochemical Research. Springer/plenum Publishers, v. 37, n. 9, n. 1967, n. 1981, 2012.
Rights: fechado
Identifier DOI: 10.1007/s11064-012-0817-y
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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