Negative modulation of inositol 1,4,5-trisphosphate type 1 receptor expression prevents dystrophin-deficient muscle cells death - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue American Journal of Physiology - Cell Physiology Année : 2009

Negative modulation of inositol 1,4,5-trisphosphate type 1 receptor expression prevents dystrophin-deficient muscle cells death

Résumé

Evidence for a modulatory effect of cyclosporin A (CsA) on calcium signaling and cell survival in dystrophin-deficient cells is presented. Our previous works strongly supported the hypothesis of an overactivation of Ca(2+) release via inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) in dystrophin-deficient cells, both during membrane depolarization and at rest, through spontaneous Ca(2+) release events. Forced expression of mini-dystrophin in these cells contributed, during stimulation and in resting condition, to the recovery of a controlled calcium homeostasis. In the present work, we demonstrate that CsA exposure displayed a dual-modulator effect on calcium signaling in dystrophin-deficient cells. Short-time incubation induced a decrease of IP3-dependent calcium release, leading to patterns of release similar to those observed in myotubes expressing mini-dystrophin, whereas long-time incubation reduced the expression of the type I of IP3 receptors (IP3R-1) RNA levels. Moreover, both IP3R-1 knockdown and blockade through 2-aminoethoxydiphenyle borate or CsA induced improved survival of dystrophin-deficient myotubes, demonstrating the cell death dependence on the IP3-dependent calcium signaling as well as the protective effect of CsA. Inhibition of the IP3 pathway could be a very interesting approach for reducing the natural cell death of dystrophin-deficient cells in development.
Fichier non déposé

Dates et versions

Identifiants

Citer

Ludivine Mondin, Haouaria Balghi, Bruno Constantin, Christian Cognard, Stéphane Sebille. Negative modulation of inositol 1,4,5-trisphosphate type 1 receptor expression prevents dystrophin-deficient muscle cells death. American Journal of Physiology - Cell Physiology, 2009, 297 (5), pp.C1133-C1145. ⟨10.1152/ajpcell.00048.2009⟩. ⟨hal-02452582⟩

Collections

CNRS UNIV-POITIERS
64 Consultations
2 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More