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| Content Provider | Springer Nature Link |
|---|---|
| Author | Rapôso, Catarina Odorissi, Paulo Alexandre Miranda Oliveira, Alexandre L. R. Aoyama, Hiroshi Ferreira, Carmen Verissima Verinaud, Liana Fontana, Karina Ruela de Sousa, Roberta R. Cruz Höfling, Maria Alice |
| Copyright Year | 2012 |
| Abstract | Phoneutria nigriventer spider venom (PNV) contains Ca$^{2+}$, 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. |
| Starting Page | 1967 |
| Ending Page | 1981 |
| Page Count | 15 |
| File Format | |
| ISSN | 03643190 |
| Journal | Neurochemical Research |
| Volume Number | 37 |
| Issue Number | 9 |
| e-ISSN | 15736903 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2012-06-09 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Astrocytes Blood–brain barrier Endothelial cells Tight and adhesion proteins Efflux protein Basement membrane Spider venom Biochemistry Cell Biology Neurology Neurochemistry Neurosciences |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Biochemistry Cellular and Molecular Neuroscience |
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