Institute of Biomedical Problems, RAS, Moscow, Russia.
Institute of Biomedical Problems, RAS, Moscow, Russia.
Free Radic Biol Med. 2024 Nov 1;224:822-830. doi: 10.1016/j.freeradbiomed.2024.10.285. Epub 2024 Oct 13.
After the first day of muscle disuse (unloading) mitochondria-derived ROS accumulate in the postural-tonic soleus muscle. It is known that excess of ROS can lead to the accumulation of intramitochondrial calcium and overload of mitochondria with calcium, can negatively affect mitochondrial function and fatigue resistance of soleus muscle. We assumed that the use of mitochondrial ROS scavenger mito-TEMPO will be able to prevent the unloading-induced disruption of mitochondrial functions and will help maintain soleus muscle fatigue resistance. To test this hypothesis, male rats were divided into 3 groups (n = 16 in each): vivarium control with placebo (C), 7-day hindlimb suspension with placebo (7HS) and 7-day hindlimb suspension with intraperitoneal administration of the mimetic superoxide dismutase mito-TEMPO at a dose of 1 mg/kg (7HSM). In the 7HS group, increased fatigue of the soleus muscle was found in the ex vivo test, accompanied with increased activity of ETC complex I and "leak" respiration, as well as a twofold increased content of oxidized tropomyosin (a marker of ROS level in tissues) and increase in intramitochondrial calcium compared to C. In 7HSM, the activity of ETC complex I and "leak" respiration had no significant differences from the control group, and the increase in intramitochondrial calcium and the content of oxidized tropomyosin was partially prevented, however, muscle fatigue was also significantly higher than in the control group. Thus, mitochondrial ROS under 7-day muscle unloading contribute to the accumulation of intramitochondrial calcium and oxidation of tropomyosin, but do not have a significant effect on soleus muscle function.
在肌肉失用（去负荷）的第一天之后，姿势性紧张的比目鱼肌中线粒体来源的 ROS 会积累。已知过量的 ROS 可导致线粒体钙积累和钙超载，从而对线粒体功能和比目鱼肌的疲劳抵抗力产生负面影响。我们假设使用线粒体 ROS 清除剂 mito-TEMPO 将能够防止去负荷引起的线粒体功能障碍，并有助于维持比目鱼肌的疲劳抵抗力。为了验证这一假设，雄性大鼠被分为 3 组（每组 16 只）：假手术对照（C）、7 天腿部悬吊（7HS）和 7 天腿部悬吊+腹腔内给予模拟超氧化物歧化酶 mito-TEMPO（1mg/kg）（7HSM）。在 7HS 组中，在离体试验中发现比目鱼肌疲劳增加，伴随着 ETC 复合物 I 活性增加和“渗漏”呼吸，以及氧化型原肌球蛋白含量增加两倍（组织中 ROS 水平的标志物）和与 C 相比，线粒体钙增加。在 7HSM 中，ETC 复合物 I 的活性和“渗漏”呼吸与对照组相比没有显著差异，并且线粒体钙的增加和氧化型原肌球蛋白的含量部分得到了预防，然而，肌肉疲劳也明显高于对照组。因此，7 天肌肉去负荷下的线粒体 ROS 有助于线粒体钙的积累和原肌球蛋白的氧化，但对比目鱼肌功能没有显著影响。
