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AHCC Supplementation Attenuates Muscle Atrophy via Akt Activation in Hindlimb-suspended Rat

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Abstract

We investigated the inhibitory effect of active hexose correlated compound (AHCC) on muscle atrophy in hindlimb-suspended rats. Twenty-four six-week-old male Sprague-Dawley rats were randomly divided into three groups: the control sedentary group (CS, n = 8), the hindlimb-suspended group (HS, n = 8), and the hindlimb-suspended and AHCC-supplemented group (HSA, n = 8). Hindlimb suspension and AHCC supplementation were performed for two weeks. The HSA group was treated with AHCC (1 g/1 kg of body weight (BW)) orally in 0.3 mL of PBS solution, while the HS group received the vehicle (PBS solution) only. After two weeks, the cross-sectional area (CSA) of the HS and HSA groups decreased by approximately 36% (p < 0.05) and 19%, respectively, compared to the CS group. In addition, myonuclear numbers of the HS and HSA groups and the extensor digitorum longus (EDL) muscle weight of the HS group decreased 30% (p < 0.05) and 18%, respectively, compared to the CS group. AHCC supplementation increased the phosphorylation of pAkt/Akt in the HSA group compared to the HS group (p < 0.05). Furthermore, Fbx32 and MuRF1 protein expression in the HSA group recovered to the level of the CS group. Based on these results, AHCC supplementation may have a positive role in the prevention of muscle atrophy via Akt activation in hindlimb-suspended rats.

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References

  1. Bodine, S. C. and L. M. Baehr (2014) Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am. J. Physiol. Endocrinol. Metab. 307: E469–484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Waters, D. L. and R. N. Baumgartner (2011) Sarcopenia and obesity. Clin. Geriatr. Med. 27: 401–42.

    Article  PubMed  Google Scholar 

  3. Dogan, M., B. Karadag, T. Ozyigit, S. Kayaoglu, A. Ozturk, Y. Altuntas (2012) Correlations between sarcopenia and hypertensive target organ damage in a Turkish cohort. Acta Clinica Belgica 67: 328–332.

    CAS  PubMed  Google Scholar 

  4. Baek, S., G. Nam, K. Han, S. Choi, S. Jung, A. Bok, Y. Kim, K. Lee, B. Han, and D. Kim (2014) Sarcopenia and sarcopenic obesity and their association with dyslipidemia in Korean elderly men: the 2008–2010 Korea National Health and Nutrition Examination Survey. J. Endocrinol. Invest. 37: 247–260.

    Article  CAS  PubMed  Google Scholar 

  5. Abbatecola, A. M., G. Paolisso, P. Fattoretti, W. J. Evans, V. Fiore, L. Dicioccio, and F. Lattanzio (2011) Discovering pathways of sarcopenia in older adults: a role for insulin resistance on mitochondria dysfunction. J. Nutr. Health Aging 15: 890–895.

    Article  CAS  PubMed  Google Scholar 

  6. Sacheck, J. M., J. P. Hyatt, A. Raffaello, R. T. Jagoe, R. R. Roy, V. R. Edgerton, S. H. Lecker, and A. L. Goldberg (2007) Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. FASEB J. 21: 140–155.

    Article  CAS  PubMed  Google Scholar 

  7. Peng, X. D., P. Z. Xu, M. L. Chen, A. Hahn-Windgassen, J. Skeen, J. Jacobs, D. Sundararajan, W. S. Chen, S. E. Crawford, K. G. Coleman, and N. Hay (2003) Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes. Dev. 17: 1352–1365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Stitt, T. N., D. Drujan, B. A. Clarke, F. Panaro, Y. Timofeyva, W. O. Kline, M. Gonzalez, G. D. Yancopoulos, and D. J. Glass (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.

    Article  CAS  PubMed  Google Scholar 

  9. Bodine, S. C., E. Latres, S. Baumhueter, V. K. Lai, L. Nunez, B. A. Clarke, W. T. Poueymirou, F. J. Panaro, E. Na, K. Dharmarajan, Z. Q. Pan, D. M. Valenzuela, T. M. DeChiara, T. N. Stitt, G. D. Yancopoulos, and D. J. Glass (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294: 1704–1708.

    Article  CAS  PubMed  Google Scholar 

  10. Gomes, M. D., S. H. Lecker, R. T. Jagoe, A. Navon, and A. L. Goldberg (2001) Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc. Natl. Acad. Sci. USA 98: 14440–14445.

    Article  CAS  PubMed  Google Scholar 

  11. Always, S. E., H. Degens, G. Krishnamurthy, and A. Chaudhrai (2003) Denervation stimulates apoptosis but not Id2 expression in hindlimb muscles of aged rats. J. Gerontol. A. Biol. Sci. Med. Sci. 58: B687–B697.

    Article  Google Scholar 

  12. Always, S. E., J. K. Martyn, J. Ouyang, A. Chaudhrai, and Z. S. Murlasits (2003) Id2 expression during apoptosis and satellite cell activation in unloaded and loaded quail skeletal muscles. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284: R540–549.

    Article  Google Scholar 

  13. Borisov, A. B. and B. M. Carlson (2000) Cell death in denervated skeletal muscle is distinct from classical apoptosis. Anat. Rec. 258: 305–318.

    Article  CAS  PubMed  Google Scholar 

  14. Léger, B., R. Senese, A.W. Al-Khodairy, O. Dériaz, C. Gobelet, J. P. Giacobino, and A. P. Russell (2009) Atrogin-1, MuRF1, and FoXO, as well as phosphorylated GSK-3β and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients. Muscle Nerve 40: 69–78.

    Article  CAS  PubMed  Google Scholar 

  15. Yoshimura, K. and K. Harii (1999) A regenerative change during muscle adaptation to denervation in rats. J. Surg. Res. 81: 139–146.

    Article  CAS  PubMed  Google Scholar 

  16. Adams, G. and F. Haddad (1996) The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy. J. Appl. Physiol. 81: 2509–2516.

    Article  CAS  PubMed  Google Scholar 

  17. Carson, J. A. (1997) The regulation of gene expression in hypertrophying skeletal muscle. Exerc. Sport Sci. Rev. 25: 301–320.

    Article  CAS  PubMed  Google Scholar 

  18. Galvan, E., E. Arentson-Lantz, S. Lamon, and D. Paddon-Jones (2016) Protecting skeletal muscle with protein and amino acid during periods of disuse. Nutrients 8: 404.

    Article  CAS  PubMed Central  Google Scholar 

  19. Gundersen, K. (2016) Muscle memory and a new cellular model for muscle atrophy and hypertrophy. J. Exp. Biol. 219: 235–242.

    Article  PubMed  Google Scholar 

  20. Matsushita, K., Y. Kuramitsu, Y. Ohiro, M. Obara, M. Kobayashi, Y. Q. Li, and M. Hosokawa (1998) Combination therapy of active hexose correlated compound plus UFT significantly reduces the metastasis of rat mammary adenocarcinoma. Anticancer Drugs 9: 343–350.

    Article  CAS  PubMed  Google Scholar 

  21. Ghoneum, M., M. Wimbley, F. Salem, A. McKlain, N. Attallah, and G. Gill (1995) Immunomodulatory and anticancer effects of active hemicellulose compound (AHCC). Int. J. Immunother. 11: 23–28.

    Google Scholar 

  22. Kidd, P. M. (2000) The use of mushroom glucans and proteoglycans in cancer treatment. Altern. Med. Rev. 5: 4–27.

    CAS  PubMed  Google Scholar 

  23. Borchers, A. T., J. S. Stern, R. M. Hackman, C. L. Keen, and M. E. Gershwin (1999) Mushrooms, tumors, and immunity. Proc. Soc. Exp. Biol. Med. 221: 281–293.

    CAS  PubMed  Google Scholar 

  24. Mizuno, T., P. Yeohlui, T. Kinoshita, C. Zhuang, H. Ito, and Y. Mayuzumi (1996) Antitumor activity and chemical modification of polysaccharides from niohshimeji mushroom, Tricholma giganteum. Biosci. Biotechnol. Biochem. 60: 30–33.

    Article  CAS  PubMed  Google Scholar 

  25. Sakagami, H., T. Aoki, A. Simpson, and S. Tanuma (1991) Induction of immunopotentiation activity by a protein-bound polysaccharide, PSK (review). Anticancer Res. 11: 993–999.

    CAS  PubMed  Google Scholar 

  26. Wasser, S. P. and A. L. Weis (1999) Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. Crit. Rev. Immunol. 19: 65–96.

    CAS  PubMed  Google Scholar 

  27. Segarra, S., G. Miro, A. Montoya, L. Pardo-Marin, J. Teichenné, L. Ferrer, and J. J. Cerón (2018) Prevention of disease progression in Leishmania infantum-infected dogs with dietary nucleotides and active hexose correlated compound. Parasit. Vectors 11: 103–112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Aviles, H., T. Belay, K. Fountain, M. Vance, and B. Sun (2003) Sonnenfeld, G. Active hexose correlated compound enhances resistance to Klebsiella pneumoniae infection in mice in the hindlimb-unloading model of spaceflight conditions. J. Appl. Physiol. 95: 491–496.

    Article  CAS  PubMed  Google Scholar 

  29. Morey-Holton, E. R. and R. K. Globus (2002) Hindlimb unloading rodent model: technical aspects. J. Appl. Physiol. 92: 1367–1377.

    Article  PubMed  Google Scholar 

  30. Bodine, S. C. and K. Baar (2012) Analysis of skeletal muscle hypertrophy in models of increased loading. Myogenesis 798: 213–229.

    Article  CAS  Google Scholar 

  31. Baghirova, S., B. G. Hughes, M. J. Hendzel, and R. Schulz (2015) Sequential fractionation and isolation of subcellular proteins from tissue or cultured cells. MethodsX 2: 440–445.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Holeček, M. and S. Mičuda (2017) Amino acid concentrations and protein metabolism of two types of rat skeletal muscle in postprandial state and after brief starvation. Physiol. Res. 66: 959–967.

    PubMed  Google Scholar 

  33. Blaauw, B., C. Marta, L. Agatea, L. Toniolo, C. Mammucari, E. Masiero, R. Abraham, M. Sandri, S. Schiaffino, and C. Reggiani (2010) Inducible activation of akt increases skeletal muscle mass and force without satellite cell activation. Biophysical. J. 98: 153a.

    Article  Google Scholar 

  34. Izumiya, Y., T. Hopkins, C. Morris, K. Sato, L. Zeng, J. Viereck, J. A. Hamilton, N. Ouchi, N. K. LeBrasseur, and K. Walsh (2008) Fast/Glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice. Cell Metab. 7: 159–172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Dong, F., Y. Hua, P. Zhao, J. Ren, M. Du, and N. Sreejayan (2009) Chromium supplement inhibits skeletal muscle atrophy in hindlimb-suspended mice. J. Nutr. Biochem. 20: 992–999.

    Article  CAS  PubMed  Google Scholar 

  36. Matsui, K., T. Ozaki, M. Oishi, Y. Tanaka, M. Kaibori, M. Nishizawa, T. Okumura, and A. H. Kwon (2011) Active hexose correlated compound inhibits the expression of proinflammatory biomarker iNOS in hepatocytes. Eur. Surg. Res. 47: 274–283.

    Article  CAS  PubMed  Google Scholar 

  37. Kadi, F., P. Schjerling, L. L. Andersen, N. Charifi, J. L. Madsen, L. R. Christensen, and J. L. Andersen (2004) The effects of heavy resistance training and detraining on satellite cells in human skeletal muscles. J. Physiol. 558: 1005–1012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lange, S., F. Xiang, A. Yakovenko, A. Vihola, P. Hackman, E. Rostkova, J. Kristensen, B. Brandmeier, G. Franzen, B. Hedberg, L. G. Gunnarsson, S. M. Hughes, S. Marchand, T. Sejersen, I. Richard, L. Edström, E. Ehler, B. Udd, and M. Gautel (2005) The kinase domain of titin controls muscle gene expression and protein turnover. Science 308: 1599–1603.

    Article  CAS  PubMed  Google Scholar 

  39. McElhinny, A. S., K. Kakinuma, H. Sorimachi, S. Labeit, and C. C. Gregorio (2002) Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and may have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1. J. Cell Biol. 157: 125–136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pizon, V., A. Iakovenko, P. F. Van Der Ven, R. Kelly, C. Fatu, D. O. Furst, E. Karsenti, and M. Gautel (2002) Transient association of titin and myosin with microtubules in nascent myofibrils directed by the MURF2 RING-finger protein. J. Cell Sci. 115: 4469–4482.

    Article  CAS  PubMed  Google Scholar 

  41. Oishi, Y., T. Ogata, K. I. Yamamoto, M. Terada, T. Ohira, Y. Ohira, K. Taniguchi, and R. R. Roy (2008) Cellular adaptations in soleus muscle during recovery after hindlimb unloading. Acta Physiol. (Oxf). 192: 381–395.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors extend their thanks to the subjects whose participation made this study possible. This work was supported by the Soonchunhyang University Research Fund.

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Correspondence to Jeong-Beom Lee.

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Song, YJ., Bae, SH., Park, JY. et al. AHCC Supplementation Attenuates Muscle Atrophy via Akt Activation in Hindlimb-suspended Rat. Biotechnol Bioproc E 24, 476–482 (2019). https://doi.org/10.1007/s12257-018-0482-3

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