Kiriaev Leonit, Perry Ben D, Mahns David A, Shortland Peter J, Redwan Asma, Morley John W, Head Stewart I
School of Medicine, Western Sydney University, Sydney, NSW, Australia.
School of Science, Western Sydney University, Sydney, NSW, Australia.
Front Physiol. 2021 Jul 5;12:696039. doi: 10.3389/fphys.2021.696039. eCollection 2021.
Minocycline, a tetracycline-class of antibiotic, has been tested with mixed effectiveness on neuromuscular disorders such as amyotrophic lateral sclerosis, autoimmune neuritis and muscular dystrophy. The independent effect of minocycline on skeletal muscle force production and signalling remain poorly understood. Our aim here is to investigate the effects of minocycline on muscle mass, force production, myosin heavy chain abundance and protein synthesis. Mice were injected with minocycline (40 mg/kg i.p.) daily for 5 days and sacrificed at day six. Fast-twitch EDL, TA muscles and slow-twitch soleus muscles were dissected out, the TA muscle was snap-frozen and the remaining muscles were attached to force transducer whilst maintained in an organ bath. In C2C12 myotubes, minocycline was applied to the media at a final concentration of 10 μg/mL for 48 h. In minocycline treated mice absolute maximal force was lower in fast-twitch EDL while in slow-twitch soleus there was an increase in the time to peak and relaxation of the twitch. There was no effect of minocycline treatment on the other contractile parameters measured in isolated fast- and slow-twitch muscles. In C2C12 cultured cells, minocycline treatment significantly reduced both myosin heavy chain content and protein synthesis without visible changes to myotube morphology. In the TA muscle there was no significant changes in myosin heavy chain content. These results indicate that high dose minocycline treatment can cause a reduction in maximal isometric force production and mass in fast-twitch EDL and impair protein synthesis during myogenesis in C2C12 cultured cells. These findings have important implications for future studies investigating the efficacy of minocycline treatment in neuromuscular or other muscle-atrophy inducing conditions.
米诺环素是一种四环素类抗生素，已针对肌萎缩侧索硬化症、自身免疫性神经炎和肌肉萎缩症等神经肌肉疾病进行了效果不一的测试。米诺环素对骨骼肌力量产生和信号传导的独立作用仍知之甚少。我们的目的是研究米诺环素对肌肉质量、力量产生、肌球蛋白重链丰度和蛋白质合成的影响。给小鼠每天腹腔注射米诺环素（40毫克/千克），持续5天，并在第6天处死。解剖出快肌趾长伸肌（EDL）、胫骨前肌（TA）和慢肌比目鱼肌，将TA肌速冻，其余肌肉连接到力传感器上，同时置于器官浴中。在C2C12肌管中，将米诺环素以终浓度10微克/毫升加入培养基中，作用48小时。在经米诺环素处理的小鼠中，快肌EDL的绝对最大力量较低，而在慢肌比目鱼肌中，抽搐达到峰值的时间和松弛时间有所增加。米诺环素处理对分离出的快肌和慢肌中测量的其他收缩参数没有影响。在C2C12培养细胞中，米诺环素处理显著降低了肌球蛋白重链含量和蛋白质合成，而肌管形态没有明显变化。在TA肌中，肌球蛋白重链含量没有显著变化。这些结果表明，高剂量米诺环素处理可导致快肌EDL的最大等长力量产生和质量降低，并损害C2C12培养细胞成肌过程中的蛋白质合成。这些发现对未来研究米诺环素治疗神经肌肉或其他肌肉萎缩诱导疾病的疗效具有重要意义。
