Institute of Biomedical Problems, RAS, 123007 Moscow, Russia.
Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine-Northwest, Gary, IN 46408, USA.
Int J Mol Sci. 2021 Sep 28;22(19):10444. doi: 10.3390/ijms221910444.
Skeletal muscle unloading results in atrophy. We hypothesized that pannexin 1 ATP-permeable channel (PANX1) is involved in the response of muscle to unloading. We tested this hypothesis by blocking PANX1, which regulates efflux of ATP from the cytoplasm. Rats were divided into six groups (eight rats each): non-treated control for 1 and 3 days of the experiments (1C and 3C, respectively), 1 and 3 days of hindlimb suspension (HS) with placebo (1H and 3H, respectively), and 1 and 3 days of HS with PANX1 inhibitor probenecid (PRB; 1HP and 3HP, respectively). When compared with 3C group there was a significant increase in ATP in soleus muscle of 3H and 3HP groups (32 and 51%, respectively, < 0.05). When compared with 3H group, 3HP group had: (1) lower mRNA expression of E3 ligases MuRF1 and MAFbx (by 50 and 38% respectively, < 0.05) and MYOG (by 34%, < 0.05); (2) higher phosphorylation of p70S6k and p90RSK (by 51 and 35% respectively, < 0.05); (3) lower levels of phosphorylated eEF2 (by 157%, < 0.05); (4) higher level of phosphorylated GSK3β (by 189%, < 0.05). In conclusion, PANX1 ATP-permeable channels are involved in the regulation of muscle atrophic processes by modulating expression of E3 ligases, and protein translation and elongation processes during unloading.
骨骼肌废用导致萎缩。我们假设缝隙连接蛋白 1 型 ATP 通透通道（PANX1）参与肌肉对废用的反应。我们通过阻断 PANX1 来测试这一假设，PANX1 调节细胞质中 ATP 的外排。大鼠分为六组（每组 8 只）：实验 1 天和 3 天的非处理对照组（分别为 1C 和 3C）、1 天和 3 天的后肢悬吊（HS）加安慰剂组（分别为 1H 和 3H）和 1 天和 3 天的 HS 加 PANX1 抑制剂丙磺舒（PRB）组（分别为 1HP 和 3HP）。与 3C 组相比，3H 和 3HP 组比目鱼肌中 ATP 含量显著增加（分别增加 32%和 51%， < 0.05）。与 3H 组相比，3HP 组：（1）E3 连接酶 MuRF1 和 MAFbx 的 mRNA 表达水平降低（分别降低 50%和 38%， < 0.05）和 MYOG（降低 34%， < 0.05）；（2）p70S6k 和 p90RSK 的磷酸化水平升高（分别升高 51%和 35%， < 0.05）；（3）磷酸化 eEF2 水平降低（降低 157%， < 0.05）；（4）磷酸化 GSK3β 水平升高（升高 189%， < 0.05）。综上所述，PANX1 型 ATP 通透通道通过调节 E3 连接酶的表达以及在卸载过程中蛋白质翻译和延伸过程，参与肌肉萎缩过程的调节。
