MBNL1-Associated Mitochondrial Dysfunction and Apoptosis in C2C12 Myotubes and Mouse Skeletal Muscle

International Journal of Molecular Sciences

HuascarPedro Ortuste Quiroga¹  Tomohiro Yamashita¹  Tatsuro Egawa¹  Rika Ito¹  Yoshitaka Ohno²  Shingo Yokoyama³  Katsumasa Goto³  Kazuya Ohashi³ 

[1] Department of Physiology, Graduate School of Health Science, Toyohashi SOZO University, Toyohashi 440-8511, Japan;Faculty of Rehabilitation and Care, Seijoh University, Tokai 476-8588, Japan;Laboratory of Physiology, School of Health Science, Toyohashi SOZO University, Toyohashi 440-8511, Japan;

关键词: MBNL1;    PGC-1α;    mitochondrial membrane potential;    apoptosis;    Bax;   

DOI  :  10.3390/ijms21176376

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown