Doctoral School, Poznan University of Physical Education, Królowej Jadwigi 27/39 Street, 61-871 Poznan, Poland.
Department of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, Dębinki 7 Street, 80-211 Gdansk, Poland.
Int J Mol Sci. 2022 Sep 29;23(19):11504. doi: 10.3390/ijms231911504.
In this study, we aim to verify whether swim training can improve lactate metabolism, NAD+ and NADH levels, as well as modify the activity of glycolytic and NADH shuttle enzymes and monocarboxylate transporters (MCTs) in skeletal muscle of amyotrophic lateral sclerosis (ALS) mice. ALS mice (SOD1G93A) (n = 7 per group) were analyzed before the onset of ALS, at first disease symptoms (trained and untrained), and the last stage of disease (trained and untrained), and then compared with a wild-type (WT) group of mice. The blood lactate and the skeletal muscle concentration of lactate, NAD+ and NADH, MCT1 and MCT4 protein levels, as well as lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) activities in skeletal muscle were determined by fluorometric, Western blotting, liquid chromatography-MS3 spectrometry, and spectrometric methods. In the untrained terminal ALS group, there were decreased blood lactate levels (p < 0.001) and increased skeletal muscle lactate levels (p < 0.05) as compared with a WT group of mice. The amount of nicotinamide adenine dinucleotides in the ALS groups were also significantly reduced as well as LDH activity and the level of MCT1. Swim training increased lactate levels in the blood (p < 0.05 vs. ALS TERMINAL untrained). In addition, cytosolic MDH activity and the cMDH/LDH 2.1 ratio were significantly higher in trained vs. untrained mice (p < 0.05). The data indicate significant dysfunction of lactate metabolism in ALS mice, associated with a reduction in muscle anaerobic metabolism and NADH transporting enzymes, as well as swim-induced compensation of energy demands in the ALS mice.
在这项研究中，我们旨在验证游泳训练是否可以改善肌萎缩侧索硬化症 (ALS) 小鼠骨骼肌中的乳酸代谢、NAD+ 和 NADH 水平，以及调节糖酵解和 NADH 穿梭酶以及单羧酸转运蛋白 (MCT) 的活性。对 SOD1G93A 型 ALS 小鼠（n = 7 只/组）进行分析，包括在 ALS 发病前、首次出现疾病症状（训练和未训练）以及疾病晚期（训练和未训练），然后与野生型 (WT) 小鼠组进行比较。通过荧光法、Western 印迹法、液相色谱-MS3 光谱法和光谱法测定骨骼肌中的血乳酸和乳酸盐浓度、NAD+ 和 NADH、MCT1 和 MCT4 蛋白水平以及乳酸脱氢酶 (LDH) 和苹果酸脱氢酶 (MDH) 活性。在未训练的终末期 ALS 组中，与 WT 小鼠组相比，血乳酸水平降低（p < 0.001），骨骼肌乳酸水平升高（p < 0.05）。ALS 组的烟酰胺腺嘌呤二核苷酸含量也显著减少，LDH 活性和 MCT1 水平降低。游泳训练增加了血液中的乳酸水平（p < 0.05 与 ALS 终末期未训练组相比）。此外，与未训练组相比，训练组的胞质 MDH 活性和 cMDH/LDH 2.1 比值显著升高（p < 0.05）。数据表明 ALS 小鼠的乳酸代谢存在明显功能障碍，与肌肉无氧代谢和 NADH 转运酶减少以及游泳诱导的 ALS 小鼠能量需求代偿有关。
