UMR 866 Différenciation Cellulaire et Croissance (INRA-UMI-UMII), Unité d'Endocrinologie Cellulaire, Institut National de la Recherche Agronomique (INRA), 2 Place Viala, 34060 Montpellier Cedex 1, France.
Exp Cell Res. 2011 Aug 15;317(14):2059-71. doi: 10.1016/j.yexcr.2011.05.020. Epub 2011 Jun 6.
We have previously shown that mitochondrial protein synthesis regulates myoblast differentiation, partly through the control of c-Myc expression, a cellular oncogene regulating myogenin expression and myoblast withdrawal from the cell cycle. In this study we provide evidence of the involvement of Calcineurin in this regulation. In C2C12 myoblasts, inhibition of mitochondrial protein synthesis by chloramphenicol decreases Calcineurin expression. Conversely, stimulation of this process by overexpressing the T3 mitochondrial receptor (p43) increases Calcineurin expression. Moreover, expression of a constitutively active Calcineurin (ΔCN) stimulates myoblast differentiation, whereas a Calcineurin antisense has the opposite effect. Lastly, ΔCN expression or stimulation of mitochondrial protein synthesis specifically increases slow myosin heavy chain expression. In conclusion, these data clearly suggest that, partly via Calcineurin expression, mitochondrial protein synthesis is involved in muscle development through the control of myoblast differentiation and probably the acquisition of the contractile and metabolic phenotype of muscle fibres.
我们之前已经表明，线粒体蛋白合成调节成肌细胞分化，部分通过控制细胞癌基因 c-Myc 的表达，该基因调节成肌细胞生成素的表达和成肌细胞退出细胞周期。在这项研究中，我们提供了钙调神经磷酸酶参与这种调节的证据。在 C2C12 成肌细胞中，氯霉素抑制线粒体蛋白合成会降低钙调神经磷酸酶的表达。相反，通过过表达 T3 线粒体受体（p43）刺激这一过程会增加钙调神经磷酸酶的表达。此外，表达组成型活性钙调神经磷酸酶（ΔCN）会刺激成肌细胞分化，而钙调神经磷酸酶反义寡核苷酸则有相反的效果。最后，ΔCN 表达或刺激线粒体蛋白合成特异性增加慢肌球蛋白重链的表达。总之，这些数据清楚地表明，线粒体蛋白合成通过控制成肌细胞分化和可能获得肌肉纤维的收缩和代谢表型，部分通过钙调神经磷酸酶的表达参与肌肉发育。
