The Effects of Lactate on Skeletal Muscle

摘要: Regular exercise and physical activity are cornerstones in the prevention treatment of numerous chronic conditions, such as type 2 diabetes, coronary heart disease, age-related sarcopenia. The associated health benefits arise from a number tissues but due to its high plasticity skeletal muscle plays pivotal role. resident stem cells tissue, so called Satellite (SCs), contribute significantly adaptation hence, maintenance healthy tissue. specific stimuli regulating SC development, i.e. activation, proliferation, an differentiation, depend on form consist hormonal, mechanical, metabolic signals. While hormonal mechanical factors have been well documented, importance Lactate (La) remains less clear. La is produced continuously under aerobic elevated levels occur during when glycolysis increased. able induce adaptation, underlying molecular mechanisms not yet understood. Therefore, one aim this study was identify phenotypical effects observed resistance or intensity endurance training proliferation differentiation model activated SCs, C2C12 cells. Furthermore, possible signalling targets for La, p38 mitogen-activated protein kinase (p38 MAPK), subsequent histone modifications were investigated. Lastly, confirm vivo, human intervention conducted. Treatment with (10 mM, 20 mM) increased serum deprivation-induced withdrawal cell cycle initiated early analysis gene expression patterns (Ki67, Trp53, Cdkn1a) markers (Pax7, Myf5, myogenin, myosin heavy chain) revealed. However, delays late dose-dependent manner. La-induced production ROS, marked by 8-epi-PGF2α levels, might at least be partly responsible induced reversible addition antioxidants ascorbic acid, N-acetylcysteine, linolenic acid. Observed downregulation MAPK activation downstream 3 lysine 4 (H3K4) 27 (H3K27) trimethylation suggests that inhibits progress mechanism which crucial transcription. Experiments using inhibitor SB203580 add further evidence hypothesis. Additionally, it demonstrated diminished conserved differentiated tissue vivo. Conclusively, reported data modifies via ROS-sensitive network delaying important adaptation. This conclusion implies reassessment traditional views design periodisation order accelerate