| Texto completo | |
| Autor(es): |
Moriscot, Anselmo S.
;
Baptista, Igor L.
;
Bogomolovas, Julius
;
Witt, Christian
;
Hirner, Stephanie
;
Granzier, Henk
;
Labeit, Siegfried
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Structural Biology; v. 170, n. 2, p. 10-pg., 2010-05-01. |
| Resumo | |
MuRF1 is a member of the RBCC (RING, B-box, coiled-coil) superfamily that has been proposed to act as an atrogin during muscle wasting. Here, we show that MuRF1 is preferentially induced in type-II muscle fibers after denervation. Fourteen days after denervation, MuRF1 protein was further elevated but remained preferentially expressed in type-II muscle fibers. Consistent with a fiber-type dependent function of MuRF1, the tibialis anterior muscle (rich in type-II muscle fibers) was considerably more protected in MuRF1-KO mice from muscle wasting when compared to soleus muscle with mixed fiber-types. We also determined fiber-type distributions in MuRF1/MuRF2 double-deficient KO (dKO) mice, because MuRF2 is a close homolog of MuRF1. MuRF1/MuRF2 dKO mice showed a profound loss of type-II fibers in soleus muscle. As a potential mechanism we identified the interaction of MuRF1/MuRF2 with myozenin-1, a calcineurin/NFAT regulator and a factor required for maintenance of type-II muscle fibers. MuRF1/MuRF2 dKO mice had lost myozenin-1 expression in tibialis anterior muscle, implicating MuRF1/MuRF2 as regulators of the calcineurin/NFAT pathway. In summary, our data suggest that expression of MuRF1 is required for remodeling of type-II fibers under pathophysiological stress states, whereas MuRF1 and MuRF2 together are required for maintenance of type-II fibers, possibly via the regulation of myozenin-1. (C) 2010 Elsevier Inc. All rights reserved. (AU) | |
| Processo FAPESP: | 07/57613-3 - Efeitos celulares e moleculares da sobrecarga de leucina na atrofia muscular induzida pelo desuso |
| Beneficiário: | Igor Luchini Baptista |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 06/61523-7 - Aspectos celulares e moleculares da plasticidade muscular |
| Beneficiário: | Anselmo Sigari Moriscot |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |