Atrophy Inhibitor
Scientists have found a way to combat skeletal muscle atrophy
RNF Press Service
Russian scientists have found out that the enzyme protein kinase GSK-3 (Glycogen Synthase Kinase-3) plays an important role in skeletal muscle atrophy in rats. If it is blocked with an inhibitor, the speed of the pathological process can be reduced. This approach will make it possible to develop new effective means of preventing ataxia in astronauts and patients of terrestrial rehabilitation centers. The results of the study, supported by a grant from the Russian Science Foundation (RNF), are published in the International Journal of Molecular Sciences (Rozhkov et al., The Role of Glycogen Synthase Kinase-3 in the Regulation of Ribosome Biogenesis in Rat Soleus Muscle under Disuse Conditions).
The role of GSK-3 activity in the suppression of ribosome biogenesis, protein synthesis and the occurrence of atrophy of flounder muscle fibers under conditions of functional unloading. Source: Timur Mirzoev
Skeletal muscles are an important part of the musculoskeletal system. They are responsible for movements, contraction of the vocal cords, breathing, and so on. In conditions of microgravity, bed rest, immobilization of limbs and artificial ventilation of the lungs, skeletal muscles are not used. Because of this, their mass, strength and overall ability to shrink can significantly decrease. Even short periods of inactivity can be dangerous, for example, for elderly people with sarcopenia — age-related muscle atrophy. Non-use of skeletal muscles for them is fraught with an increased risk of falls, fractures, the development of metabolic diseases and other negative health consequences.
In this regard, it is important to investigate the processes leading to muscular atrophy. The main ones are considered to be slowing down the synthesis and simultaneous acceleration of the breakdown of muscle protein. The rate of its formation largely depends on the number of ribosomes in muscle fibers. It is with the help of these intracellular structures that new proteins from amino acids are created in the body. The formation of new ribosomes (biogenesis) is a complex cellular process that requires the work of many different enzymes. It is thanks to him that after strength training, proteins in the muscles are synthesized more intensively, as a result of which muscle mass grows. During functional unloading, for example, during long inactivity, the reverse process occurs — ribosome biogenesis and protein synthesis decreases, both in rats and in humans. However, the molecular mechanisms of such events remained unexplored. Today it is only known that the enzyme glycogen synthase-3 kinase (GSK-3) can play an important role in the process.
Scientists from The Institute of Biomedical Problems of the Russian Academy of Sciences (Moscow) found out that the GSK-3 protein kinase inhibitor partially prevents a decrease in muscle protein synthesis during the period of muscle inactivity. Biologists conducted a study on male rats in which the flounder muscles located on the back of the lower leg were subjected to various loads. So, as part of the experiment, the animals were randomly divided into four groups. In the first, the rats had a natural weight load in the form of their own body — they sat and walked on the floor of the cage, — in the second, in addition, they received injections of a GSK-3 inhibitor. In the third, the animals were suspended in such a way as to "unload" the hind limbs, and in the fourth, in addition to hanging, they were also injected with the drug.
After seven days of the experiment, the flounder muscles of the rats were cut out and frozen in liquid nitrogen. Cross sections of the resulting muscle tissue were specially stained and photographed under a fluorescent microscope to analyze the diameter of the fibers. In addition, using molecular methods, scientists determined the rate of protein synthesis, as well as the number of ribosome precursor molecules in cells, which allowed us to assess how fast the biogenesis of these structures is going.
It turned out that the mass of the flounder muscles in rats from the third group, which did not experience any loads, decreased by 27%, and the diameter of muscle fibers decreased by almost 40%. In addition, the "unloading" of the hind limbs reduced the rate of protein synthesis in the flounder muscle by 82% compared to rats from the control group whose hind limbs were under load. The introduction of the GSK-3 inhibitor against the background of functional unloading allowed to suspend the degradation process by 22%, due to which the cross-sectional area of muscle fibers decreased not so much.
"The study suggests that GSK-3 may become a promising molecular target for the treatment of muscle atrophy caused by prolonged inactivity. This will prevent this pathology in patients who are forced to observe prolonged bed rest, as well as in astronauts who spend an average of six months in zero gravity," comments Timur Mirzoev, project manager for the RNF grant, senior researcher at the Institute of Biomedical Problems of the Russian Academy of Sciences.
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