Antioxidant Mito-TEMPO Partially Prevents Rat Soleus Muscle Atrophy after 7 Days of Functional Unloading

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Abstract

Functional unloading of skeletal muscles is observed during spaceflight, prolonged bed rest, or limb immobilization. In this case, skeletal muscle atrophy develops, which is a serious consequence for health and a noticeable decrease in quality of life. In addition, during functional unloading, mitochondrial dysfunction is observed and the release of reactive oxygen species (ROS) by mitochondria increases. It is known that some antioxidants can reduce the manifestation of atrophy during functional unloading. We hypothesized that the mitochondrial-specific antioxidant Mito-TEMPO would block the accumulation of mitochondrial ROS, which would lead to the prevention of an increase in ubiquitin ligase mRNA expression and prevent a decrease in anabolic parameters during 7-day functional unloading, which together could inhibit atrophy development. To test the hypothesis, we used a 7-day rat hindlimb suspension model of functional unloading. In our study, animals treated with Mito-TEMPO during 7-day suspension partially prevented the decrease in soleus muscle fiber cross-sectional area, the increase in the expression of in MuRF-1 and Atrogin mRNA expression, and the decrease in the content of rRNA. In addition, Mito-TEMPO reduced ROS-dependent oxidation of tropomyosin during 7-day suspension in the rat soleus muscle. Thus, the accumulation of mitochondrial ROS in the soleus muscle during 7-day functional unloading affects both protein synthesis and degradation, which is reflected in a decrease in muscle fiber cross-sectional area in the rat soleus muscle.

About the authors

D. A. Sidorenko

Institute of Biomedical Problems of the Russian Academy of Sciences

Email: darya.si.00@mail.ru
Moscow, Russia

I. D. Lvova

Institute of Biomedical Problems of the Russian Academy of Sciences

Moscow, Russia

B. S. Shenkman

Institute of Biomedical Problems of the Russian Academy of Sciences

Moscow, Russia

K. A. Sharlo

Institute of Biomedical Problems of the Russian Academy of Sciences

Moscow, Russia

References

  1. Morey-Holton E.R., Globus R.K. 2002. Hindlimb unloading rodent model: technical aspects. J. Appl. Physiol. (1985). 92, 1367–1377. https://doi.org/10.1152/japplphysiol.00969.2001
  2. Ильин Е.А., Новиков В.Е. 1980. Стенд для моделирования физиологических эффектов невесомости в лабораторных условиях. Косм. биол. мед. 14, 79–80.
  3. Tyganov S.A., Mochalova E.P., Belova S.P., Sharlo K.A., Rozhkov S.V., Vilchinskaya N.A., Paramonova I.I., Mirzoev T.M., Shenkman B.S. 2019. Effects of plantar mechanical stimulation on anabolic and catabolic signaling in rat postural muscle under short-term simulated gravitational unloading. Front Physiol. 10, 1252. https://doi.org/10.3389/fphys.2019.01252
  4. Rozhkov S.V., Sharlo K.A., Mirzoev T.M., Shenkman B.S. 2021. Temporal changes in the markers of ribosome biogenesis in rat soleus muscle under simulated microgravity. Acta Astronaut. 186, 252–258. https://doi.org/10.3390/ijms2305275
  5. Ferrando A.A., Lane H.W., Stuart C.A., Davis-Street J., Wolfe R.R. 1996. Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am. J. Physiol. 270, E627–E633. https://doi.org/10.1152/ajpendo.1996.270.4.E627.
  6. Mirzoev T.M., Shenkman B.S., Ushakov I.B., Ogneva I.V. 2012. Desmin and α-actinin-2 content in rat soleus muscle in the dynamics of gravitational unloading and subsequent reloading. Dokl. Biochem. Biophys. 444, 144–146. https://doi.org/10.1134/S1607672912030052
  7. Ogneva I.V. 2010. Transversal stiffness of fibers and desmin content in leg muscles of rats under gravitational unloading of various durations. J. Appl. Physiol. 109, 1702–1709. https://doi.org/10.1152/japplphysiol.00793.2010
  8. Ferreira R., Vitorino R., Neuparth M.J., Appell H.J., Duarte J.A., Amado F. 2009. Proteolysis activation and proteome alterations in murine skeletal muscle submitted to 1 week of hindlimb suspension. Eur. J. Appl. Physiol. 107, 553–563. https://doi.org/10.1007/s00421-009-1151-1
  9. Baehr L.M., West D.W.D., Marshall A.G., Marcotte G.R., Baar K., Bodine S.C. 2017. Muscle-specific and age-related changes in protein synthesis and protein degradation in response to hindlimb unloading in rats. J. Appl. Physiol (1985). 122, 1336–1350. https://doi.org/10.1152/japplphysiol.00703.2016
  10. Trevino M.B., Zhang X., Standley R.A., Wang M., Han X., Reis F.C.G., Periasamy M., Yu G., Kelly D.P., Goodpaster B.H., Vega R.B., Coen P.M. 2019. Loss of mitochondrial energetics is associated with poor recovery of muscle function but not mass following disuse atrophy. Am. J. Physiol. Endocrinol. Metab. 317, E899–E910. https://doi.org/10.1152/ajpendo.00161.2019
  11. Appell H.J., Duarte J.A.R., Soares J.M.C. 1997. Supplementation of vitamin E may attenuate skeletal muscle immobilization atrophy. Int. J. Sports Med. 18, 157–160. https://doi.org/10.1055/s-2007-972612
  12. Min K., Smuder A.J., Kwon O.S., Kawazis A.N., Szeto H.H., Powers S.K. 2011. Mitochondrial-targeted antioxidants protect skeletal muscle against immobilization-induced muscle atrophy. J. Appl. Physiol. 111, 1459–1466. https://doi.org/10.1152/japplphysiol.00591.2011
  13. Lechado i Terradas A., Vitadello M., Traini L., Namuduri A.V., Gastaldello S., Gorza L. 2018. Sarcolemmal loss of active nNOS (Nos1) is an oxidative stress-dependent, early event driving disuse atrophy. J. Pathol. 246, 433–446. https://doi.org/10.1002/path.5149
  14. Pfaffl M.W. 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29, E45. https://doi.org/10.1093/nar/29.9.e45
  15. Templeton G.H., Sweeney H.L., Timson B.F., Padalino M., Dudenhoeffer G.A. 1988. Changes in fiber composition of soleus muscle during rat hindlimb suspension. J. Appl. Physiol. (1985). 65, 1191–1195. https://doi.org/10.1152/jappl.1988.65.3.1191
  16. Thomason D.B., Booth F.W. 1990. Atrophy of the soleus muscle by hindlimb unweighting. J. Appl. Physiol. (1985). 68, 1–12. https://doi.org/10.1152/jappl.1990.68.1.1
  17. Vitadello M., Germinario E., Ravara B., Libera L.D., Danieli-Betto D., Gorza L. 2014. Curcumin counteracts loss of force and atrophy of hindlimb unloaded rat soleus by hampering neuronal nitric oxide synthase untethering from sarcolemma. J. Physiol. 592, 2637–2652. https://doi.org/10.1113/jphysiol.2013.268672
  18. Bodine S.C., Latres E., Baumhueter S., Lai V.K., Nunez L., Clarke B.A., Poueymirou W.T., Panaro F.J., Na E., Dharmarajan K. et al. 2001. Identification of ubiquitin ligases required for skeletal Muscle Atrophy. Science. 294, 1704–1708. https://doi.org/10.1126/science.1065874
  19. Stitt T.N., Drujan D., Clarke B.A., Panaro F., Timofeyva Y., Kline W.O., Gonzalez M., Yancopoulos G.D., Glass D.J. 2004. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol. Cell. 14, 395–403. https://doi.org/10.1016/s1097-2765(04)00211-4
  20. Millward D.J., Garlick P.J., James W.P.T., Nnanyelugo D.O., Ryatt J.S. 1973. Relationship between protein synthesis and RNA content in skeletal muscle. Nature. 241, 204–205. https://doi.org/10.1038/241204a0
  21. Kimball S.R., Jefferson L.S. 2010. Control of translation initiation through integration of signals generated by hormones, nutrients, and exercise. J. Biol. Chem. 285, 29027. https://doi.org/10.1074/jbc.R110.137208
  22. von Walden F., Liu C., Aurigemma N., Nader G.A. 2016. mTOR signaling regulates myotube hypertrophy by modulating protein synthesis, rDNA transcription, and chromatin remodeling. Am. J. Physiol. Cell Physiol. 311, C663–C672. https://doi.org/10.1152/ajpcell.00144.2016

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