| Texto completo | |
| Autor(es): Mostrar menos - |
Trujillo, Cleber A.
[1]
;
Negraes, Priscilla D.
[1]
;
Schwindt, Telma T.
[1]
;
Lameu, Claudiana
[1]
;
Carromeu, Cassiano
[2, 3]
;
Muotri, Alysson R.
[2, 3]
;
Pesquero, Joao B.
[4]
;
Cerqueira, Debora M.
[5]
;
Pillat, Micheli M.
[1]
;
de Souza, Hellio D. N.
[1]
;
Turaca, Lauro T.
[4]
;
Abreu, Jose G.
[5]
;
Ulrich, Henning
[1]
Número total de Autores: 13
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo - Brazil
[2] Univ Calif San Diego, Dept Pediat, San Diego, CA 92093 - USA
[3] Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA 92093 - USA
[4] Univ Fed Sao Paulo, Dept Biofis, BR-04023062 Sao Paulo - Brazil
[5] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, BR-21941902 Rio De Janeiro - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Biological Chemistry; v. 287, n. 53, p. 44046-44061, DEC 28 2012. |
| Citações Web of Science: | 24 |
| Resumo | |
Bradykinin is not only important for inflammation and blood pressure regulation, but also involved in neuromodulation and neuroprotection. Here we describe novel functions for bradykinin and the kinin-B2 receptor (B2BkR) in differentiation of neural stem cells. In the presence of the B2BkR antagonist HOE-140 during rat neurosphere differentiation, neuron-specific beta 3-tubulin and enolase expression was reduced together with an increase in glial protein expression, indicating that bradykinin- induced receptor activity contributes to neurogenesis. In agreement, HOE-140 affected in the same way expression levels of neural markers during neural differentiation of murine P19 and human iPS cells. Kinin-B1 receptor agonists and antagonists did not affect expression levels of neural markers, suggesting that bradykinin-mediated effects are exclusively mediated via B2BkR. Neurogenesis was augmented by bradykinin in the middle and late stages of the differentiation process. Chronic treatment with HOE-140 diminished eNOS and nNOS as well as M1-M4 muscarinic receptor expression and also affected purinergic receptor expression and activity. Neurogenesis, gliogenesis, and neural migration were altered during differentiation of neurospheres isolated from B2BkR knock-out mice. Whole mount in situ hybridization revealed the presence of B2BkR mRNA throughout the nervous system in mouse embryos, and less beta 3-tubulin and more glial proteins were expressed in developing and adult B2BkR knock-out mice brains. As a underlying transcriptional mechanism for neural fate determination, HOE-140 induced up-regulation of Notch1 and Stat3 gene expression. Because pharmacological treatments did not affect cell viability and proliferation, we conclude that bradykinin-induced signaling provides a switch for neural fate determination and specification of neurotransmitter receptor expression. (AU) | |
| Processo FAPESP: | 06/61285-9 - Bases moleculares da diferenciação de células-tronco e progenitoras neurais |
| Beneficiário: | Alexander Henning Ulrich |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |