Swim Training Affects on Muscle Lactate Metabolism, Nicotinamide Adenine Dinucleotides Concentration, and the Activity of NADH Shuttle Enzymes in a Mouse Model of Amyotrophic Lateral Sclerosis

• Published in: International journal of molecular sciences 2022-09, Vol.23 (19), p.11504
• Main Authors: Cieminski, Karol, Flis, Damian Jozef, Dzik, Katarzyna Patrycja, Kaczor, Jan Jacek, Wieckowski, Mariusz Roman, Antosiewicz, Jedrzej, Ziolkowski, Wieslaw
• Format: Article
• Language: English
• Subjects: Adenine; Adenine - metabolism; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - metabolism; Animals; Blood; Dehydrogenases; Disease Models, Animal; Enzymes; Glycolysis; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Lactic Acid - metabolism; Liquid chromatography; Malate dehydrogenase; Malate Dehydrogenase - metabolism; Metabolism; Mice; Mitochondria; Monocarboxylic Acid Transporters - metabolism; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; NAD - metabolism; NADH; Niacinamide - metabolism; Nicotinamide; Proteins; Rodents; Signs and symptoms; Skeletal muscle; Spectrometry; Spinal cord; Western blotting
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.