Estudo do mecanismo de ação do veneno da aranha Phoneutria nigriventer na barreira...
Análise da flutuação do Ca2+ intracelular e de marcadores inflamatórios em astróci...
Caveolae as a target for Phoneutria nigriventer spider venom
| Texto completo | |
| Autor(es): |
Raposo, Catarina
[1]
;
Miranda Odorissi, Paulo Alexandre
[1]
;
Oliveira, Alexandre L. R.
[2]
;
Aoyama, Hiroshi
[3]
;
Ferreira, Carmen Verissima
[3]
;
Verinaud, Liana
[2]
;
Fontana, Karina
[4]
;
Ruela-de-Sousa, Roberta R.
[3]
;
da Cruz-Hoefling, Maria Alice
[1]
Número total de Autores: 9
|
| Afiliação do(s) autor(es): | [1] Univ Estadual Campinas UNICAMP, Dept Histol & Embriol, Inst Biol, BR-13087130 Campinas, SP - Brazil
[2] Univ Estadual Campinas UNICAMP, Dept Biol Estrutural & Func, Inst Biol, BR-13087130 Campinas, SP - Brazil
[3] Univ Estadual Campinas UNICAMP, Dept Bioquim, Inst Biol, BR-13087130 Campinas, SP - Brazil
[4] Univ Estadual Campinas UNICAMP, Dept Farmacol, Fac Ciencias Med, BR-13087130 Campinas, SP - Brazil
Número total de Afiliações: 4
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Neurochemical Research; v. 37, n. 9, p. 1967-1981, SEP 2012. |
| Citações Web of Science: | 20 |
| Resumo | |
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. (AU) | |
| Processo FAPESP: | 08/55748-1 - Veneno e toxina da aranha Phoneutria nigriventer: ação no sistema nervoso central |
| Beneficiário: | Maria Alice da Cruz Hofling |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 98/00341-0 - Estudo da acao nefrotoxica do veneno de bothrops moojeni "in vivi" em rim isolado e cultura de celulas renais. |
| Beneficiário: | Maria Alice da Cruz Hofling |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |