| Texto completo | |
| Autor(es): |
Soares, Edilene Siqueira
[1]
;
Padilha Mendonca, Monique Culturato
[1, 2]
;
da Cruz-Hofling, Maria Alice
[1, 2]
Número total de Autores: 3
|
| Afiliação do(s) autor(es): | [1] State Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, BR-13083970 Campinas, SP - Brazil
[2] State Univ Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, BR-13083970 Campinas, SP - Brazil
Número total de Afiliações: 2
|
| Tipo de documento: | Artigo Científico |
| Fonte: | NeuroToxicology; v. 54, p. 111-118, MAY 2016. |
| Citações Web of Science: | 5 |
| Resumo | |
An important transcellular transport mechanism in the blood-brain barrier (BBB) involves caveolae, which are specialized delta-shaped domains of the endothelial plasma membrane that are rich in cholesterol, glycosphingolipids and the scaffolding protein Caveolina-1 (Cav-1). In this work, we investigated whether the increase in endocytosis and transendothelial vesicular trafficking in rat cerebellum after blood-brain barrier breakdown (BBBb) induced by Phoneutria nigriventer spider venom (PNV) was mediated by caveolae. The expression of Cav-1, phosphorylated Cav-1 (pCav-1), dynamin-2 (Dyn2), Src kinase family (SKF) and matrix-metalloproteinase-9 (MMP9), proteins involved in caveolar dynamics and BBB opening, was investigated. Immunofluorescence, western blotting (WB) and transmission electron microscopy were used to assess changes at 1, 2, 5, 24 and 72 h post-venom. WB showed upregulation of Cav-1, Dyn2 and MMP9 at 1, 5 and 72 h (corresponding, respectively, to intervals when intoxication was most evident, when signs of recovery were present, and when no intoxication was detectable). In contrast, pCav-1 and SKF, which are essential for internalization and transport, decreased when Cav-1 and Dyn2, proteins essential for caveolar formation, were increased. Overall, these changes indicated that vesicular trafficking across the endothelium (high pCav/SKF levels) coincided with lower numbers of caveolae (Cav-1/Dyn2 downregulation) and lower expression of MMP9. Thus, the internalization (disassembly) of caveolae alternates with caveolar neoformation (assembly), resulting in changes in caveolar density in the endothelium membrane. These caveolar dynamics imply tensional mechanical stress that is important in triggering key signaling mechanisms. We conclude that PNV-induced breakdown of transcellular transport in the BBB is caused by an increase in caveolae-mediated endocytosis; this effect was correlated with the progression of temporal signs of envenoming. Caveolar dynamics are probably involved in shear stress and BBBb regulatory mechanisms in this experimental model. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). (AU) | |
| Processo FAPESP: | 05/53625-1 - Ação dos mastoparanos e da fosfolipase A2 isolados do veneno de Polybia paulista (Hymenoptera, Epiponini) nos mecanismos de apoptose e necrose de células musculares e mitocôndrias isoladas de camundongos Balb/c |
| Beneficiário: | Maria Alice da Cruz Hofling |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 12/24782-5 - Óxido de grafeno e sistema nervoso central: avaliação dos efeitos na barreira hematoencefálica e perfil nanotoxicológico |
| Beneficiário: | Monique Culturato Padilha Mendonça |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |