Skip to main content
SpringerLink
Log in

Physiological basis of the pathogenesis of alcohol-induced skeletal muscle injury

  • Reviews
  • Published:
Human Physiology Aims and scope Submit manuscript

Abstract

Alcohol-induced muscle damage (AIMD) is an umbrella term that includes all forms of alcoholic myopathy developing in acute or chronic alcohol intoxication. The most common form of destruction of skeletal muscles in alcoholism is chronic alcoholic myopathy, which develops independently of other alcohol-induced disorders, such as polyneuropathy, the malabsorption syndrome, and liver damage, but may be combined with them. The atrophy of muscle fibers underlies skeletal muscle destruction in chronic AIMD. Type II muscle fibers are affected to a greater degree than type I muscle fibers. To date, the pathogenesis of chronic alcoholic myopathy has been studied insufficiently. The imbalance between protein synthesis and proteolysis, as well as increased apoptosis rate, is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zinov’eva, O.E. and Shenkman, B.S., Alcoholic myopathy, Nevrol. Zh., 2007, no. 5, p. 4.

    Google Scholar 

  2. Rubenstein, A.E. and Wainapel, S.F., Acute hypokalemic myopathy in alcoholism. a clinical entity, Arch. Neurol., 1977, vol. 34, p. 553.

    Article  CAS  PubMed  Google Scholar 

  3. Kishore, B., Thurlow, V., and Kessel, B., Hypokalaemic rhabdomyolysis, Ann. Clin. Biochem., 2007, vol. 44, p. 308.

    Article  CAS  PubMed  Google Scholar 

  4. Showalter, C.J. and Engel, A.G., Acute quadriplegic myopathy: analysis of myosin isoforms and evidence for calpain-mediated proteolysis, Muscle Nerve, 1997, vol. 20, p. 316.

    Article  CAS  PubMed  Google Scholar 

  5. Vary, T.C., Frost, R.A., and Lang, C.H., Acute alcohol intoxication increases atrogin-1 and MuRF1 mRNA without increasing proteolysis in skeletal muscle, Am. J. Physiol.: Regul. Integr. Comp. Physiol., 2008, vol. 294, p. 1777.

    Google Scholar 

  6. Gekht, B.M., Kasatkina, L.F., Samoilov, M.I., and Sanadze, A.G., Electromyography in the Diagnosis of Neuromuscular Disease, Taganrog: Taganrog. Gos. Radiotekh. Univ., 1997.

    Google Scholar 

  7. Hong-Brown, L.Q., Frost, R.A., and Lang, C.H., Alcohol impairs protein synthesis and degradation in cultured skeletal muscle cells, Alcohol. Clin. Exp. Res., 2001, vol. 25, p. 1373.

    Article  CAS  PubMed  Google Scholar 

  8. Koll, M., Ahmed, S., Mantle, D., et al., Effect of acute and chronic alcohol treatment and their superimposition on lysosomal, cytoplasmic, and proteosomal protease activities in rat skeletal muscle in vivo, Metabolism, 2002, vol. 51, no. 1, p. 97.

    Article  CAS  PubMed  Google Scholar 

  9. Fernandez-Sola, J., Nicolas, J.M., Sacanella, E., et al., Low-dose ethanol consumption allows strength recovery in chronic alcoholic myopathy, Q. J. Med., 2000, vol. 93, p. 35.

    Article  CAS  Google Scholar 

  10. Preedy, V.R., Ohlendieck, K., Adachi, J., et al., The importance of alcohol-induced muscle disease, J. Muscle Res. Cell Motil., 2003, vol. 24, no. 1, p. 55.

    Article  CAS  PubMed  Google Scholar 

  11. Fernández-Solà, J., Nicolás, J.M., Fatjó, F., et al. Evidence of apoptosis in chronic alcoholic skeletal myopathy, Hum. Pathol., 2003, vol. 34, p. 1247.

    Article  PubMed  Google Scholar 

  12. Steiner, J.L. and Lang, C.H., Dysregulation of skeletal muscle protein metabolism by alcohol, Am. J. Physiol. Endocrinol. Metab., 2015, vol. 308, no. 9, p. E699.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Shenkman, B.S., Lomonosova, Yu.N., Lysenko, E.A., et al., Proteolytic signaling mechanisms in skeletal muscles in patients with alcohol-induced muscle disease, Hum. Physiol., 2013, vol. 39, no. 5, p. 545.

    Article  CAS  Google Scholar 

  14. Burnham, E.L., Moss, M., and Ziegler, T.R., Myopathies in critical illness: characterization and nutritional aspects, J. Nutr., 2005, vol. 135, p. 1818.

    Google Scholar 

  15. Paice, A.G., Hesketh, J.E., Towner, P., and Hirako, M., No change of apoptosis in skeletal muscle exposed acutely or chronically to alcohol, Addict. Biol., 2003, vol. 8, no. 1, p. 97.

    Article  CAS  PubMed  Google Scholar 

  16. Shcheglova, N.S., Altaeva, E.G., Zinov’eva, O.E., et al., Impairment of the peripheral nerves and skeletal muscles in women suffering from chronic alcohol intoxication, Med. Sov., 2013, no. 4, p. 64.

    Google Scholar 

  17. Ammendola, A., Gemini, D., Iannaccone, S., et al., Gender and peripheral neuropathy in chronic alcoholism: a clinical-electroneurographic study, Alcohol Alcohol., 2000, vol. 35, p. 368.

    Article  CAS  PubMed  Google Scholar 

  18. Lang, C.H., Frost, R.A., Svanberg, E., and Vary, T.C., IGF-1/IGFBP-3 ameliorates alterations in protein synthesis, eIF4E availability, and myostatin in alcoholfed rats, Am. J. Physiol., 2004, vol. 286, p. E916.

    CAS  Google Scholar 

  19. Hunter, R.J., Neagoe, C., Jarvelainen, H.A., et al., Alcohol affects the skeletal muscle proteins, titin and nebulin in male and female rats, J. Nutr., 2003, vol. 133, p. 1154.

    CAS  PubMed  Google Scholar 

  20. Lysenko, E.A., Kazantseva, Yu.V., Zinov’eva, O.E., et al., Cellular signalling mechanisms in development of atrophy of human skeletal muscles at chronic and alcohol myopathy, Tekhnol. Zhivykh Sist., 2010, vol. 7, no. 8, p. 38.

    CAS  Google Scholar 

  21. Lang, C.H., Frost, R.A., Summer, A.D., et al., Molecular mechanisms responsible for alcohol-induced myopathy in skeletal muscle and heart, Int. J. Biochem. Cell Biol., 2005, vol. 37, p. 2180.

    Article  CAS  PubMed  Google Scholar 

  22. Otis, J.S., Brown, L.A.S., and Guidot, D.M., Oxidantinduced atrogin-1 and transforming growth factor-β1 precede alcohol-related myopathy in rats, Muscle Nerve, 2007, vol. 36, no. 6, p. 842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lang, C.H., Fan, J., Lipton, B.P., et al., Modulation of the insulin-like growth factor system by chronic alcohol feeding, Alcohol. Clin. Exp. Res., 1998, vol. 22, p. 823.

    Article  CAS  PubMed  Google Scholar 

  24. Frost, R.A. and Lang, C.H., Regulation of insulin-like growth factor-I in skeletal muscle and muscle cells, Minerva Endocrinol., 2002, vol. 28, p. 53.

    Google Scholar 

  25. Nguyen, V.A., Le, T., Tong, M., et al. Insulin/IGF signaling in experimental alcohol-related myopathy, Nutrients, 2012, vol. 4, p. 1058.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lang, C.H. and Frost, R.A., Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection. Anabolic and catabolic signals, Curr. Opin. Clin. Nutr. Metab. Care, 2002, vol. 5, no. 3, p. 271.

    Article  CAS  PubMed  Google Scholar 

  27. Soliman, G.A., Acosta-Jaquez, H.A., Dunlop, E.A., et al., mTOR Ser-2481 autophosphorylation monitors mTORC-specific catalytic activity and clarifies rapamycin mechanism of action, J. Biol. Chem., 2010, vol. 285, p. 7866.

    Article  CAS  PubMed  Google Scholar 

  28. Preedy, V.R., Peters, T.J., Patel, V.B., et al., Chronic alcoholic myopathy: transcription and translational alterations, The FASEB J., 1994, no. 8, p. 1146.

    CAS  PubMed  Google Scholar 

  29. Lang, C.H., Frost, R.A., Deshpande, N., et al., Alcohol impairs leucine-mediated phosphorylation of 4EBP1, S6K1, eIF4G, and mTOR in skeletal muscle, Am. J. Physiol.: Endocrinol. Metab., 2003, vol. 285, no. 6, p. 1205.

    Article  Google Scholar 

  30. Polak, P. and Hall, M.N., mTOR and the control of whole body metabolism, Curr. Opin. Cell Biol., 2009, vol. 21, p. 209.

    Article  CAS  PubMed  Google Scholar 

  31. Lang, C.H., Pruznak, A.M., Deshpande, N., et al., Alcohol intoxication impairs phosphorylation of S6K1 and S6 in skeletal muscle independently of ethanol metabolism, Alcohol.: Clin. Exp. Res., 2004, vol. 28, p. 3922.

    Google Scholar 

  32. Lang, C.H., Pruznak, A.M., Nystrom, G.J., and Vary, T.C., Alcohol-induced decrease in muscle protein synthesis associated with increased binding of mTOR and raptor: comparable effects in young and mature rats, Nutr. Metab., 2009, vol. 6, p. 4.

    Article  Google Scholar 

  33. Powers, T., TOR signaling and S6 kinase 1: yeast catches up, Cell Metab., 2007, vol. 6, no. 1, p. 1.

    Article  CAS  PubMed  Google Scholar 

  34. Pacy, P.J., Preedy, V.R., Peters, T.J., et al., The effect of chronic alcohol ingestion on whole body and muscle protein synthesis—a stable isotope study, Alcohol, 1991, vol. 26, p. 505.

    CAS  Google Scholar 

  35. Vary, T.C., Nairn, A.C., and Lang, C.H., Restoration of protein synthesis in heart and skeletal muscle after withdrawal of alcohol, Alcohol.: Clin. Exp. Res., 2004, vol. 28, p. 517.

    Article  CAS  Google Scholar 

  36. Anthony, J.C., Yoshizawa, F., Anthony, T.G., et al., Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway, J. Nutr., 2000, vol. 130, p. 2413.

    CAS  PubMed  Google Scholar 

  37. Kimball, S.R. and Jefferson, L.S., Role of amino acids in the translational control of protein synthesi in muscle, Semin. Cell Dev. Biol., 2005, vol. 16, p. 21.

    Article  CAS  PubMed  Google Scholar 

  38. Pruznak, A.M., Nystrom, J., and Lang, C.H., Direct central nervous system effect of alcohol alters synthesis and degradation of skeletal muscle protein, Alcohol Alcohol., 2013, vol. 48, no. 2, p. 138.

    Article  CAS  PubMed  Google Scholar 

  39. Fernández-Solà, J., Lluis, M., and Sacanella, E., Increased myostatin activity and decreased myocyte proliferation in chronic alcoholic cardiomyopathy, Alcohol.: Clin. Exp. Res., 2011, vol. 35, p. 1220.

    Article  Google Scholar 

  40. Arya, M.A., Tai, A.K., and Wooten, E.C., Notch pathway activation contributes to inhibition of C2C12 myoblast differentiation by ethanol, PLoS One, 2013, vol. 20, no. 8.

    Google Scholar 

  41. Goodman, C.A. and Hornberger, T.A., New roles for Smad signaling and phosphatidic acid in the regulation of skeletal muscle mass, F1000Prime Rep., 2014, vol. 6, p. 20.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Lang, C.H., Frost, R.A., Nairn, A.C., et al., TNF alpha impairs heart and skeletal muscle protein synthesis by altering translation initiation, Am. J. Physiol.: Endocrinol. Metab., 2002, vol. 282, p. E336.

    CAS  Google Scholar 

  43. Gorlach, A., Klappa, P., and Kietzmann, T., The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control, Antioxid. Redox Signaling, 2006, vol. 8, nos. 9–10, p. 1391.

    Article  Google Scholar 

  44. Preedy, V.R., Crabb, D.W., Farres, J., et al., Alcoholic myopathy and acetaldehyde, Novartis Found. Symp., 2007, vol. 285, p. 158.

    Article  CAS  PubMed  Google Scholar 

  45. Preedy, V.R., Keating, J.W., and Peters, T.J., The acute effects of ethanol and acetaldehyde on rates of protein synthesis in type I and type II fibre-rich skeletal muscles of the rat, Alcohol Alcohol., 1992, vol. 27, no. 3, p. 241.

    CAS  PubMed  Google Scholar 

  46. Cardellach, F., Galofre, J., Grau, J.M., et al., Oxidative metabolism in muscle mitochondria from patients with chronic alcoholism, Ann. Neurol., 1992, vol. 31, p. 515.

    Article  CAS  PubMed  Google Scholar 

  47. Lang, C.H., Wu, D., Frost, R.A., et al., Inhibition of muscle protein synthesis by alcohol is associated with modulation of eIF2B and eIF4E, Am. J. Physiol., 1999, vol. 277, p. E268.

    CAS  PubMed  Google Scholar 

  48. Jacobsen, E.B., Hamberg, O., Quistorff, B., and Ott, P., Reduced mitochondrial adenosine triphosphate synthesis in skeletal muscle in patients with Child-Pugh class B and C cirrhosis, Hepatology, 2001, vol. 34, p. 7.

    Article  CAS  PubMed  Google Scholar 

  49. Eisner, V., Lenaers, G., and Hajnoczky, G., Mitochondrial fusion is frequent in skeletal muscle and supports excitation-contraction coupling, J. Cell Biol., 2014, vol. 205, p. 179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. González-Reimers, E., Santolaria-Fernández, F., Martín-González, M.C., et al., Alcoholism: a systemic proinflammatory condition, World J. Gastroenterol., 2014, vol. 20, no. 40, p. 14660.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Koo-Ng, R., Falkous, G., Reilly, M., et al., Carbonyl levels in type I and II fiber-rich muscles and their response to chronic ethanol feeding in vivo and hydroxyl and superoxide radicals in vitro, Alcohol.: Clin. Exp. Res., 2000, vol. 24, p. 1862.

    Article  CAS  Google Scholar 

  52. Fernandez-Sola, J., Garcia, G., Elena, M., et al., Muscle antioxidant status in chronic alcoholism, Alcohol.: Clin. Exp. Res., 2002, vol. 26, p. 1858.

    Article  CAS  Google Scholar 

  53. Otis, J.S. and Guidot, D.M., Procysteine increases alcohol-depleted glutathione stores in rat plantaris following a period of abstinence, Alcohol Alcohol., 2010, vol. 45, p. 495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Otis, J.S. and Guidot, D.M., Procysteine stimulates expression of key anabolic factors and reduces plantaris atrophy in alcohol-fed rats, Alcohol.: Clin. Exp. Res., 2009, vol. 33, p. 1450.

    Article  CAS  Google Scholar 

  55. González-Reimers, E. and Durán-Castellón, M.C., López-Lirola A. et al. Alcoholic myopathy: vitamin D deficiency is related to muscle fibre atrophy in a murine model, Alcohol Alcohol., 2010, vol. 45, p. 223.

    Article  PubMed  Google Scholar 

  56. Nicolas, J.M., Garcia, G., Fatjy, F., et al., Influence of nutritional status on alcoholic myopathy, Am. J. Clin. Nutr., 2003, vol. 78, p. 326.

    CAS  PubMed  Google Scholar 

  57. Wijnia, J.W., Wielders, J.P., Lips, P., et al., Is vitamin D deficiency a confounder in alcoholic skeletal muscle myopathy?, Alcohol.: Clin. Exp. Res., 2012, vol. 37, suppl. 1, p. E209.

    Google Scholar 

  58. Durán Castellón, M.C. and González-Reimers, E., López-Lirola, A., Alcoholic myopathy: lack of effect of zinc supplementation, Food Chem. Toxicol., 2005, vol. 43, p. 1333.

    Article  PubMed  Google Scholar 

  59. Koll, M., Beeso, J.A., Kelly, F.J., and Simanowski, U.A., Chronic alphatocopherol supplementation in rats does not ameliorate either chronic or acute alcohol-induced changes in muscle protein metabolism, Clin. Sci., 2003, vol. 104, p. 287.

    Article  CAS  PubMed  Google Scholar 

  60. Pirlich, M., Kiok, K., Sandig, G., et al., Alpha-lipoic acid prevents ethanol-induced protein oxidation in mouse hippocampal HT22 cells, Neurosci. Lett., 2002, vol. 328, no. 2, p. 93.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sechenov First State Medical University, Moscow, Russia

    O. E. Zinovyeva, A. Yu. Emelyanova, N. D. Samkhaeva & N. S. Shcheglova

  2. Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia

    B. S. Shenkman & T. L. Nemirovskaya

  3. Moscow State University, Moscow, Russia

    T. L. Nemirovskaya

Authors
  1. O. E. Zinovyeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Yu. Emelyanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. D. Samkhaeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. S. Shcheglova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. S. Shenkman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. L. Nemirovskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. E. Zinovyeva.

Additional information

Original Russian Text © O.E. Zinovyeva, A.Yu. Emelyanova, N.D. Samkhaeva, N.S. Shcheglova, B.S. Shenkman, T.L. Nemirovskaya, 2016, published in Fiziologiya Cheloveka, 2016, Vol. 42, No. 3, pp. 130–136.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zinovyeva, O.E., Emelyanova, A.Y., Samkhaeva, N.D. et al. Physiological basis of the pathogenesis of alcohol-induced skeletal muscle injury. Hum Physiol 42, 343–349 (2016). https://doi.org/10.1134/S0362119716020171

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0362119716020171

Keywords

Search

Navigation