Artículos de revistas
Effect Of Phoneutria Nigriventer Venom On The Expression Of Junctional Protein And P-gp Efflux Pump Function In The Blood-brain Barrier
Registro en:
Neurochemical Research. , v. 37, n. 9, p. 1967 - 1981, 2012.
3643190
10.1007/s11064-012-0817-y
2-s2.0-84866742503
Autor
Raposo C.
Odorissi P.A.M.
Oliveira A.L.R.
Aoyama H.
Ferreira C.V.
Verinaud L.
Fontana K.
Ruela-De-Sousa R.R.
Da Cruz-Hofling M.A.
Institución
Resumen
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. 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