Korean Journal of Agricultural Science (농업과학연구)

Institute of Agricultural Science, CNU (충남대학교 농업과학연구소)
권호 표지
DOI QR코드

DOI QR Code

Inhibition of mitochondrial activity induces muscle fiber type change from slow to fast in C2C12 myotubes

  • Received : 2017.08.18
  • Accepted : 2017.11.20
  • Published : 2017.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Mitochondrial activity affects skeletal muscle energy metabolism and phenotype. To address whether mitochondrial activity can modulate muscle phenotype in vitro, protein expression of myosin heavy chain (MyHC) in C2C12 muscle cell lines was investigated after treated with antimycin A, an inhibitor of oxidative phosphorylation in mitochondria. Fully differentiated C2C12 myotubes were administrated with different concentration of antimycin A including 0, 100, 200, 500, 700, and 1000 ng/mL. After 72 h treatment, myosin heavy chain isoform expression and related enzyme activity (lactate dehydrogenase; LDH and creatine kinase) were analyzed. Administration of antimycin A changed expression of MyHC in C2C12 myotubes showing a shift from slow to fast twitching muscle type. Protein expression of MyHC type 2b (fast twitching muscle type) was decreased (P < 0.05) by antimycin A treatment (500, 700, and 1000 ng/mL) when compared with control group. Administration of antimycin A (1000 ng/mL), however, decreased (P < 0.05) MyHC type I (slow twitching muscle type). Interestingly, LDH activity was increased (P < 0.05) by antimycin A treatment. Results from our current study proposed a possibility that skeletal muscle phenotype, including MyHC and LDH activity, can be shifted from slow to fast twitching type by inhibiting the mitochondrial activity in C2C12 myotubes.

Keywords

References

  1. Booth RF, Clark JB. 1978. Studies on the mitochondrially bound form of rat brain creatine kinase. Biochemistry Journal 170:145-151. https://doi.org/10.1042/bj1700145
  2. Dickman KG, Mandel LJ. 1990. Differential effects of respiratory inhibitors on glycolysis in proximal tubules. American Journal of Physiology - Renal Physiology 258:F1608-F1615. https://doi.org/10.1152/ajprenal.1990.258.6.F1608
  3. Gunawan AM, Park SK, Pleitner JM, Feliciano L, Grant AL, Gerrard DE. 2007. Contractile protein content reflects myosin heavy-chain isoform gene expression. Journal Animal Science 85:1247-1256. https://doi.org/10.2527/jas.2006-511
  4. Han YH, Kim SH, Kim SZ, Park WH. 2008. Antimycin A as a mitochondrial electron transport inhibitor prevents the growth of human lung cancer A549 cells. Oncology Reports 20:689-693.
  5. Handschin C, Chin S, Li P, Liu F, Maratos-Flier E, Lebrasseur NK, Yan Z, Spiegelman BM. 2007. Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals. Journal Biological Chemistry 282:30014-30021. https://doi.org/10.1074/jbc.M704817200
  6. Jansson E, Esbjornsson M, Holm I, Jacobs I. 1990. Increase in the proportion of fast-twitch muscle fibres by sprint training in males. Acta Physiologica Scandinavica 140:359-363. https://doi.org/10.1111/j.1748-1716.1990.tb09010.x
  7. Lim D, Song M, Lee J, Lee C, Lee J, Lee W, Seo J, Jung S. 2016. Characteristic of back fat and quality of longissimus dorsi muscle from soft fat pork carcasses. Korean Journal of Agricultural Science 12:581-588.
  8. Liu J, Liang X, Zhou D, Lai L, Xiao L, Liu L, Fu T, Kong Y, Zhou Q, Vega RB, Zhu MS, Kelly DP, Gao X, Gan Z. 2016. Coupling of mitochondrial function and skeletal muscle fiber type by a miR‐499/Fnip1/AMPK circuit. EMBO Molecular Medicine 8:1212-1228. https://doi.org/10.15252/emmm.201606372
  9. Matsakas A, Patel K. 2009. Skeletal muscle fibre plasticity in response to selected environmental and physiological stimuli. Histology and Histopathology 24:611-629.
  10. Meyer LE, Machado LB, Santiago APSA, da-Silva WS, De Felice FG, Holub O, Oliveira MF, Galina A. 2006. Mitochondrial Creatine Kinase Activity Prevents Reactive Oxygen Species Generation: ANTIOXIDANT ROLE OF MITOCHONDRIAL KINASE-DEPENDENT ADP RE-CYCLING ACTIVITY. Journal of Biological Chemistry 281:37361-37371. https://doi.org/10.1074/jbc.M604123200
  11. Morgan JE, Partridge TA. 2003. Muscle satellite cells. International Journal Biochem and Cell Biology 35:1151-1156. https://doi.org/10.1016/S1357-2725(03)00042-6
  12. Pette D, Staron RS. 2000. Myosin isoforms, muscle fiber types, and transitions. Microscopy Research and Technique 50:500-509. https://doi.org/10.1002/1097-0029(20000915)50:6<500::AID-JEMT7>3.0.CO;2-7
  13. Ryu JH, Lee YK, Cho SB, Hwang OH, Park SK. 2016. Effect of metabolic imprinting on growth and development in piglets. Korean Journal of Agricultural Science 43:72-79. https://doi.org/10.7744/kjoas.20160009
  14. Scheffler TL, Park S, Roach PJ, Gerrard DE. 2016. Gain of function AMP-activated protein kinase ${\gamma}3$ mutation ($AMPK{\gamma}$ 3R200Q) in pig muscle increases glycogen storage regardless of AMPK activation. Physiological Reports 4:1-9.
  15. Schiaffino S, Reggiani C. 1994. Myosin isoforms in mammalian skeletal muscle. Journal Applied Physiology 77:493-501. https://doi.org/10.1152/jappl.1994.77.2.493
  16. Schiaffino S, Reggiani C. 1996. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiological Reviews 76:371-423. https://doi.org/10.1152/physrev.1996.76.2.371
  17. Seifert EL, Bastianelli M, Aguer C, Moffat C, Estey C, Koch LG, Britton SL, Harper ME. 2012. Intrinsic aerobic capacity correlates with greater inherent mitochondrial oxidative and $H_2O_2$ emission capacities without major shifts in myosin heavy chain isoform. Journal Applied Physiology 113:1624-1634. https://doi.org/10.1152/japplphysiol.01475.2011
  18. Tepp K, Shevchuk I, Chekulayev V, Timohhina N, Kuznetsov AV, Guzun R, Saks V, Kaambre T. 2011. High efficiency of energy flux controls within mitochondrial interactosome in cardiac intracellular energetic units. Biochimica et Biophysica Acta (BBA) - Bioenergetics 1807:1549-1561. https://doi.org/10.1016/j.bbabio.2011.08.005
  19. Toyama EQ, Herzig S, Courchet J, Lewis TL, Jr., Loson OC, Hellberg K, Young NP, Chen H, Polleux F, Chan DC, Shaw RJ. 2016. Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science 351:275-281. https://doi.org/10.1126/science.aab4138
  20. Wallimann T, Tokarska-Schlattner M, Schlattner U. 2011. The creatine kinase system and pleiotropic effects of creatine. Amino Acids 40:1271-1296. https://doi.org/10.1007/s00726-011-0877-3
  21. Westerblad H, Bruton JD, Katz A. 2010. Skeletal muscle: energy metabolism, fiber types, fatigue and adaptability. Experimental Cell Research 316:3093-3099. https://doi.org/10.1016/j.yexcr.2010.05.019

Cited by

  1. Overview of muscle metabolism, muscle fiber characteristics, and meat quality vol.45, pp.1, 2017, https://doi.org/10.7744/kjoas.20180012