Myology Laboratory, Institute of Biomedical Problems RAS, 123007 Moscow, Russia.
Cells. 2023 Mar 16;12(6):920. doi: 10.3390/cells12060920.
Regrowth of atrophied myofibers depends on muscle satellite cells (SCs) that exist outside the plasma membrane. Muscle atrophy appears to result in reduced number of SCs due to apoptosis. Given reduced AMP-activated protein kinase (AMPK) activity during differentiation of primary myoblasts derived from atrophic muscle, we hypothesized that there may be a potential link between AMPK and susceptibility of differentiating myoblasts to apoptosis. The aim of this study was to estimate the effect of AMPK activation (via AICAR treatment) on apoptosis in differentiating myoblasts derived from atrophied rat soleus muscle. Thirty rats were randomly assigned to the following two groups: control (C, n = 10) and 7-day hindlimb suspension (HS, n = 20). Myoblasts derived from the soleus muscles of HS rats were divided into two parts: AICAR-treated cells and non-treated cells. Apoptotic processes were evaluated by using TUNEL assay, RT-PCR and WB. In differentiating myoblasts derived from the atrophied soleus, there was a significant decrease ( < 0.05) in AMPK and ACC phosphorylation in parallel with increased number of apoptotic nuclei and a significant upregulation of pro-apoptotic markers (caspase-3, -9, BAX, p53) compared to the cells derived from control muscles. AICAR treatment of atrophic muscle-derived myoblasts during differentiation prevented reductions in AMPK and ACC phosphorylation as well as maintained the number of apoptotic nuclei and the expression of pro-apoptotic markers at the control levels. Thus, the maintenance of AMPK activity can suppress enhanced apoptosis in differentiating myoblasts derived from atrophied rat soleus muscle.
萎缩肌纤维的再生依赖于存在于细胞膜外的肌肉卫星细胞（SCs）。肌肉萎缩似乎导致 SC 数量减少，这是由于细胞凋亡所致。鉴于源自萎缩肌肉的原代肌细胞分化过程中 AMP 激活蛋白激酶（AMPK）活性降低，我们假设 AMPK 和分化中的肌细胞对细胞凋亡的易感性之间可能存在潜在联系。本研究的目的是评估 AMPK 激活（通过 AICAR 处理）对源自萎缩大鼠比目鱼肌的分化肌细胞凋亡的影响。30 只大鼠随机分为以下两组：对照组（C，n = 10）和 7 天后肢悬吊（HS，n = 20）。来自 HS 大鼠比目鱼肌的肌细胞分为两部分：AICAR 处理的细胞和未处理的细胞。通过 TUNEL 检测、RT-PCR 和 WB 评估凋亡过程。在源自萎缩比目鱼肌的分化肌细胞中，AMPK 和 ACC 磷酸化显著降低（<0.05），同时凋亡核数量增加，促凋亡标志物（caspase-3、-9、BAX、p53）表达显著上调，与源自对照肌肉的细胞相比。在分化过程中，用 AICAR 处理源自萎缩肌肉的肌细胞可防止 AMPK 和 ACC 磷酸化减少，并将凋亡核数量和促凋亡标志物的表达维持在对照水平。因此，维持 AMPK 活性可以抑制源自萎缩大鼠比目鱼肌的分化肌细胞中增强的细胞凋亡。
