Laboratory of Physiology, School of Health Science, Toyohashi SOZO University, Toyohashi 440-8511, Japan.
Faculty of Rehabilitation and Care, Seijoh University, Tokai 476-8588, Japan.
Int J Mol Sci. 2020 Sep 2;21(17):6376. doi: 10.3390/ijms21176376.
We explored the interrelationship between a tissue-specific alternative splicing factor muscleblind-like 1 (MBNL1) and peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α), B-cell lymphoma 2 (Bcl-2) or Bcl-2-associated X protein (Bax) in C2C12 myotubes and mouse skeletal muscle to investigate a possible physiological role of MBNL1 in mitochondrial-associated apoptosis of skeletal muscle. Expression level of PGC-1α and mitochondrial membrane potential evaluated by the fluorescence ratio of JC-1 aggregate to monomer in C2C12 myotubes were suppressed by knockdown of MBNL1. Conversely, the ratio of Bax to Bcl-2 as well as the apoptotic index in C2C12 myotubes was increased by MBNL1 knockdown. In plantaris muscle, on the other hand, not only the minimum muscle fiber diameter but also the expression level of MBNL1 and PGC-1α in of 100-week-old mice were significantly lower than that of 10-week-old mice. Furthermore, the ratio of Bax to Bcl-2 in mouse plantaris muscle was increased by aging. These results suggest that MBNL1 may play a key role in aging-associated muscle atrophy accompanied with mitochondrial dysfunction and apoptosis via mediating PGC-1α expression in skeletal muscle.
我们探讨了组织特异性剪接因子肌肉萎缩蛋白 1（MBNL1）与过氧化物酶体增殖物激活受体γ共激活因子 1-α（PGC-1α）、B 细胞淋巴瘤 2（Bcl-2）或 Bcl-2 相关 X 蛋白（Bax）之间的相互关系，在 C2C12 肌管和小鼠骨骼肌中，以研究 MBNL1 在骨骼肌线粒体相关凋亡中的可能生理作用。用 JC-1 聚集体与单体的荧光比值评估 C2C12 肌管中的 PGC-1α 和线粒体膜电位的表达水平，均受到 MBNL1 敲低的抑制。相反，MBNL1 敲低后 C2C12 肌管中 Bax 与 Bcl-2 的比值以及凋亡指数增加。另一方面，在比目鱼肌中，不仅 100 周龄小鼠的最小肌纤维直径，而且 MBNL1 和 PGC-1α 的表达水平均明显低于 10 周龄小鼠。此外，小鼠比目鱼肌中 Bax 与 Bcl-2 的比值随年龄增长而增加。这些结果表明，MBNL1 可能通过调节骨骼肌中 PGC-1α 的表达，在与年龄相关的肌肉萎缩伴线粒体功能障碍和凋亡中发挥关键作用。
