DOI QR코드

DOI QR Code

Dexamethasone으로 유도한 근위축 세포모델에서 흑효모 배양물 유래 polycan의 근위축 개선에 대한 효과

Effects of polysaccharide (polycan) derived from black yeast in dexamethasone-induced muscle atrophy cell model

  • Hwang, Su-Jin (Department of Pharmaceutical Engineering, Daegu Haany University) ;
  • Lim, Jong-Min (Glucan Co. Ltd.) ;
  • Ku, Bon-Hwa (Glucan Co. Ltd.) ;
  • Cheon, Da-Mi (Glucan Co. Ltd.) ;
  • Jung, Yu Jin (Research Center for Advanced Specialty Chemicals, Korea Research Institute of Chemical Technology (KRICT)) ;
  • Kim, Young-Suk (Glucan Co. Ltd.) ;
  • Oh, Tae Woo (Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM))
  • 투고 : 2021.02.08
  • 심사 : 2021.02.21
  • 발행 : 2021.02.28

초록

Objectives : This study was conducted to evaluate the anti-atrophic effect of polycan in dexamethasone-induced skeletal muscle atrophy in vitro model. Methods : C2C12 myoblast were differentiated into myotube by 2% horese serum medium for 6 days, and then treated polycan extract at different concentrations for 24h. The effect of dexamethasone on the induction of muscle atrophy and expression of atrophy-related genes in differentiated C2C12 myotubes using a GSH, ROS, real-time PCR, western blots analysis. Results : The results showed that Treatment with polycan (100 and 200 ㎍/㎖) noncytotoxic levels on both myoblast and myotube. Polycan decreased the ROS level overproduced with dexamethasone and improved the depletion of GSH level. Dexamethasone showed a decrease in myotube diameter, which was associated with up-regulation muscle-specific ubiquitin ligases markers, such as atrogin-1, FoxO3, myostatin and muscle RING finger-1 (MuRF1), and down-regulation of myogenin, MEF2, Myogenic regulatory factor 5, 6 and MyoD. The results showed that polycan treatment significantly dose-dependently inhibited it. Furthermore, decreased expressions of PI3K/Akt signal pathway by dexamethasone were reversed by treatment with polycan. Conclusions : Thus, polycan suppresses dexamethasone induced muscle atrophy in C2C12 myotube in vitro model through activation of PI3K/Akt pathway and protective effect of improve skeletal muscle function.

키워드

참고문헌

  1. Jagoe RT, Goldberg AL. What do we really know about the ubiquitin-proteasome pathway in muscle atrophy?. Curr Opin Clin Nutr Metab Care. 2001;4:183-190. https://doi.org/10.1097/00075197-200105000-00003
  2. Ammar A, Turki M, Chtourou H, Hammouda O, Trabelsi K, Kallel C, Abdelkarim O, Hoekelmann A, Bouaziz M, Ayadi F, Driss T, Souissi N. Pomegranate Supplementation Accelerates Recovery of Muscle Damage and Soreness and Inflammatory Markers after a Weightlifting Training Session. PLoS One. 2016;11(10)
  3. Kandarian, SC, Jackman RW. Intracellular signaling during skeletal muscle atrophy. Muscle Nerve. 2006;33:155-165. https://doi.org/10.1002/mus.20442
  4. Jesinkey SR, Korrapati MC, Rasbach, KA, Beeson CC, Schnellmann RG. Atomoxetine prevents dexamethasone-induced skeletal muscle atrophy in mice. J Pharmacol Exp Ther. 2014;351:663-673. https://doi.org/10.1124/jpet.114.217380
  5. Marinovic AC, Zheng B, Mitch WE, Price SR. Tissue-specific regulation of ubiquitin (UbC) transcription by glucocorticoids: in vivo and in vitro analyses. Am J Physiol Renal Physiol. 2007;292:F660-666. https://doi.org/10.1152/ajprenal.00178.2006
  6. Denison HJ, Cooper C, Sayer AA, Robinson SM. Prevention and optimal management of sarcopenia: a review of combined exercise and nutrition interventions to improve muscle outcomes in older people. Clin Interv Aging. 2015;10:859-69.
  7. Li YP, Chen Y, Li AS, Reid MB. Hydrogen peroxide stimulates ubiquitin-conjugating activity and expression of genes for specific E2 and E3 proteins in skeletal muscle myotubes. Am J Physiol Cell Physiol. 2003;285:C806-812. https://doi.org/10.1152/ajpcell.00129.2003
  8. Lawler JM, Song W, Demaree SR. Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle. Free Radic Biol Med. 2003;35:9-16. https://doi.org/10.1016/S0891-5849(03)00186-2
  9. Habukuihakwon. youngchu-kyungkyosuk. Beijing: Inminwisheng publisher; 1982:161.24
  10. Chan GCF, Chan WK, Sze DMY: The effect of β-glucan on human immune and cancer cells. J Hematol Oncol. 2009;2:1-11. https://doi.org/10.1186/1756-8722-2-1
  11. Song HS, Moon KY: In vitro antioxidant activity profiles of β-glucan isolated from yeast Saccharomayces cerevisiae and mutant Saccharomayces cerevisiae IS2. Food Sci Biotechnol. 2006;15:437-440.
  12. Novak M, Vetvicka V: Beta-glucans, history, and the present: immunomodulatory aspects and mechanisms of action. J Immunotoxicol. 2008;5:47-57. https://doi.org/10.1080/15476910802019045
  13. Tecucianu JF: Double-blind clinical study of a titrated extract of an unsaponifiable fraction of Zea mays (L) on gingival inflammation. Inf Dent. 1975;57:21-32.
  14. Shin HD, Yang KJ, Park BR, Son CW, Jang HJ, Ku SK: Antiosteoporotic effect of polycan, beta-glucan from Aureobasidium, in ovariectomized osteoporotic mice. Nutrition. 2007;23:853-860. https://doi.org/10.1016/j.nut.2007.08.011
  15. Song HB, Park DC, Do GM, et al.: Effect of exopolymers of Aureobasidium pullulans on improving osteoporosis induced in ovariectomized mice. J Microbiol Biotechnol. 2006;16: 37-45.
  16. Chan GC, Chan WK, Sze DM. The effects of beta-glucan on human immune and cancer cells. J. Hematol. Oncol. 2009;2:doi: 10.1186/1756-8722-2-25.
  17. Kim JH, Kim KR, Jin HJ, Im SU, Song KB, Choi YH. The Effect of Polycan-Calcium Gluconate Complex on Inflammatory Mediators from Periodontitis Patients. J Dent Hyg Sci. 2014;14(2):223-229.
  18. Seo HP, Kim JM, Shin HD, Kim TK, Chang HJ, Park BR, Lee JW. Production of β-1,3/1,6-glucan by Aureobasidium pullulans SM-2001. Kor J Biotechnol Bioeng. 2002; 17:376-380.
  19. Faulkner JA, Larkin LM, Claflin DR, Brooks SV. Age-related changes in the structure and function of skeletal muscles. Clin. Exp Pharmacol Physiol. 2007;34(11):1091-1096. https://doi.org/10.1111/j.1440-1681.2007.04752.x
  20. Cebron Lipovec N, Schols AMWJ, van den Borst B, Beijers RJHCG, Kosten T, Omersa D, Lainscak M. Sarcopenia in advanced COPD affects cardiometabolic risk reduction by shortterm high-intensity pulmonary rehabilitation. J Am Med Dir Assoc. 2016;17(9):814-820. https://doi.org/10.1016/j.jamda.2016.05.002
  21. Park SH, Park JH, Song PS, Kim DK, Kim KH, Seol SH, Kim HK, Jang HJ, Lee JG, Park HY, Park JS, Shin KJ, Kim DI, Moon YS. Sarcopenic obesity as an independent risk factor of hypertension. J Am Soc Hypertens. 2013;7(6):420-425. https://doi.org/10.1016/j.jash.2013.06.002
  22. Kim JK, Choi SR, Choi MJ, Kim SG, Lee YK, Noh JW, Kim HJ, Song YR. Prevalence of and factors associated with sarcopenia in elderly patients with end-stage renal disease. Clin Nutr Edinb Scotl. 2014;33(1):64-68. https://doi.org/10.1016/j.clnu.2013.04.002
  23. Kraus J, Blaschek W, Schutz M, Franz G. Antitumor activity of cell wall β-1,3/1,6-glucans from Phytophthora species. Planta Medica. 1992;58:39-42. https://doi.org/10.1055/s-2006-961386
  24. Keum BR, Hyeon JY, Choe SH, Jin JY, Jeong JW, Lim JM, Park DH, Cho KK, Choi EY, Choi IS. β-glucan Stimulates Release of TNF-α in Human Monocytic THP-1 Cells. J Life Sci. 2017;27(11):1256-1261. https://doi.org/10.5352/JLS.2017.27.11.1256
  25. Esther A, Joan AB, Josep R, Jose CF. Glutathione Depletion Impairs Myogenic Differentiation of Murine Skeletal Muscle C2C12 Cells through Sustained NF-κB Activation. Am J Pathol. 2004;165(3):719-728. https://doi.org/10.1016/S0002-9440(10)63335-4
  26. Bentzinger CF, Wang YX, Rudnicki MA. Building muscle: molecular regulation of myogenesis. Cold Spring Harb Perspect Biol. 2012;4(2). pii:a008342.
  27. Song MY. Effect of Root of Atractylodes macrocephala Koidzumi on myogenesis in C2C12 cells. J Korean Med Obes Res. 2015;15:38-44. https://doi.org/10.15429/jkomor.2015.15.1.38
  28. Kovacheva EL, Hikim AP, Shen R, Sinha I, Sinha-Hikim I. Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology 2010;151:628-638. https://doi.org/10.1210/en.2009-1177
  29. Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci USA. 2001;98:14440-14445. https://doi.org/10.1073/pnas.251541198