Homoarginine and ornithine production during C2C12 myogenic differentiation

  • Alexandr Zhloba Biochemical Department of Scientific Centre, Pavlov First Saint Petersburg State Medical University, L'va Tolstogo Str., 6–8, Saint Petersburg, 197022, Russian Federation https://orcid.org/0000-0003-0605-7617
  • Tatiana Subbotina Biochemical Department of Scientific Centre, Pavlov First Saint Petersburg State Medical University, L'va Tolstogo Str., 6–8, Saint Petersburg, 197022, Russian Federation https://orcid.org/0000-0002-2278-8391
  • Stanislava Prikhodko Institute of Molecular Biology and Genetics, Almazov Federal Medical Research Centre, ul. Akkuratova, 2, Saint Petersburg, 197341, Russian Federation https://orcid.org/0000-0001-7018-6398
  • Alexandr Khudiakov Institute of Molecular Biology and Genetics, Almazov Federal Medical Research Centre, ul. Akkuratova, 2, Saint Petersburg, 197341, Russian Federation
  • Natalia Smolina Institute of Molecular Biology and Genetics, Almazov Federal Medical Research Centre, ul. Akkuratova, 2, Saint Petersburg, 197341, Russian Federation; ITMO University, Saint Petersburg, Russian Federation https://orcid.org/0000-0002-3339-0688
  • Anna Kostareva Institute of Molecular Biology and Genetics, Almazov Federal Medical Research Centre, ul. Akkuratova, 2, Saint Petersburg, 197341, Russian Federation; ITMO University, Saint Petersburg, Russian Federation; Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden https://orcid.org/0000-0002-9349-6257

Abstract

Assessment of cellular rates of amino acid consumption and release in vitro allows the study of cell culture in a time-course experiment without any cell damage. Determination of the release of amino acid metabolites that initially were not present in the media provides more reliable information about the processes of growth and differentiation in comparison with determination of amino acid consumption rates. Homoarginine (hArg), a derivative of arginine, is generated as the minor product in the reaction catalyzed by L-Arginine: glycine amidinotransferase, where L-lysine serves as an acceptor for amidine group instead of glycine. Ornithine is another product generated in this reaction from arginine. Thus, the goal of the present study was to evaluate the rate of hArg and ornithine accumulation in comparison to the rate of consumption of other amino acids in the course of C2C12 myoblast differentiation. The release time profiles were similar for hArg and ornithine, with the maximum corresponding to the second day of differentiation. The shift for hArg at this time point was detected with greater reliability (p < 0.002) than for ornithine and other amino acids. We suggest that hArg and ornithine could serve as markers to monitor the processes of myoblasts growth and differentiation.

Keywords:

amino acids, homoarginine, myogenic differentiation, ornithine

Downloads

Download data is not yet available.

References

Atzler, D., Gore, M. O., Ayers, C. R., Choe, C. U., Böger, R. H., de Lemos, J. A., McGuire, D. K., and Schwedhelm, E. 2014. Homoarginine and Cardiovascular Outcome in the Population-Based Dallas Heart Study. Arteriosclerosis Thrombosis and Vascular Biology 34:2501−2507. https://doi.org/10.1161/ATVBAHA.114.304398

Braissant, O., Henry, H., Villard, A. M., Speer, O., Wallimann, T., and Bachmann, C. 2005. Creatine synthesis and transport during rat embryogenesis: spatiotemporal expression of AGAT, GAMT and CT1. BMC Developmental Biology 5:9. https://doi.org/10.1186/1471-213X-5-9

Burattini, S., Ferri, P., Battistelli, M., Curci, R., Luchetti, F., and Falcieri, E. 2004. C2C12 murine myoblasts as a model of skeletal muscle development: morpho-functional characterization. European Journal of Histochemistry 48:223−234. https://doi.org/10.4081/891

Carrillo-Cocom, L. M., Genel-Rey, T., Araíz-Hernández, D., López-Pacheco, F., López-Meza, J., Rocha-Pizaña, M. R., Ramirez-Medrano, A., and Alvarez, M. M. 2015. Amino acid consumption in naïve and recombinant CHO cell cultures: producers of a monoclonal antibody. Cytotechnology 67(5):809–820. https://doi.org/10.1007/s10616-014-9720-5

Choe, C. U., Atzler, D., Wild, P. S., Carter, A. M., Böger, R. H., Ojeda, F., Simova, O., Stockebrand, M., Lackner, K., Nabuurs, C., Marescau, B., Streichert, T., Müller, C., Lüneburg, N., De Deyn, P. P., Benndorf, R. A., Baldus, S., Gerloff, C., Blankenberg, S., Heerschap, A., Grant, P. J., Magnus, T., Zeller, T., Isbrandt, D., and Schwedhelm, E. 2013. Homoarginine levels are regulated by L-arginine:glycine:amidinotransferase and affect stroke outcome: results from human and murine studies. Circulation 128:1451−1461. https://doi.org/10.1161/CIRCULATIONAHA.112.000580

Cullen, M. E., Yuen, A. H., Felkin, L. E., Smolenski, R. T., Hall, J. L., Grindle, S., Miller, L. W., Birks, E. J., Yacoub, M. H., and Barton, P. J. 2006. Myocardial expression of the arginine:glycine:amidinotransferase gene is elevated in heart failure and normalized after recovery: potential implications for local creatine synthesis. Circulation 114:16−20. https://doi.org/10.1161/CIRCULATIONAHA.105.000448

Davids, M., Ndika, J. D. T., Salomons, G. S., Blom, H. J., and Teerlink, T. 2012. Promiscuous activity of arginine:glycine:amidinotransferase is responsible for the synthesis of the novel cardiovascular risk factor homoarginine. Federation of European Biochemical Societies Letters 586:3653−3657. https://doi.org/10.1016/j.febslet.2012.08.020

Drechsler, C., Meinitzer, A., Pilz, S., Krane, V., Tomaschitz, A., Ritz, E., März, W., and Wanner, C. 2011. Homoarginine, heart failure, and sudden cardiac death in haemodialysis patients. European Journal of Heart Failure 13(8):852−859. https://doi.org/10.1093/eurjhf/hfr056

Henderson, J. W., Ricker, R. D., Bidlingmeyer, B. A., Woodward, C. 2000. Rapid, accurate, sensitive and reproducible HPLC analysis of amino acids. Agilent Pub 5980-1193 E

Hong, P., Wheat, T. E., Mazzeo, J. R., and Diehl, D. M. 2007. Monitoring cell culture media with the Waters amino acid analysis solution. Waters Applications Notebook 720002381EN

Hou, Y., Jia, S., Nawaratna, G., Hu, S., Dahanayaka, S., Bazer, F. W., and Wu, G. 2015. Analysis of L-homoarginine in biological samples by HPLC involving precolumn derivatization with o-phthalaldehyde and N-acetyl-L-cysteine. Amino Acids 47(9):2005−2014. https://doi.org/10.1007/s00726-015-1962-9

Hou, Y., Hu, S., Jia, S., Nawaratna, G., Che, D., Wang, F., Bazer, F. W., and Wu, G. 2016. Whole-body synthesis of L-homoarginine in pigs and rats supplemented with L-arginine. Amino Acids 48(4):993−1001. https://doi.org/10.1007/s00726-015-2145-4

Keire, P., Shearer, A., Shefer, G., and Yablonka-Reuveni, Z. 2013. Isolation and culture of skeletal muscle myofibers as a means to analyze satellite cells. Methods Mol Biol 946:431–468. https://doi.org/10.1007/978-1-62703-128-8_28

März, W., Meinitzer, A., Drechsler, C., Pilz, S., Krane, V., Kleber, M. E., Fischer, J., Winkelmann, B. R., Böhm, B. O., Ritz, E., and Wanner, C. 2010. Homoarginine, cardiovascular risk, and mortality. Circulation 122(10):967−975. https://doi.org/10.1161/CIRCULATIONAHA.109.908988

Salazar, A., Keusgen, M., and von Hagen, J. 2016. Amino acids in the cultivation of mammalian cells. Amino Acids 48(5):1161−1171. https://doi.org/10.1007/s00726-016-2181-8

Sandell, L. L., Guan, X. J., Ingram, R., and Tilghman, S. M. 2003. Gatm, a creatine synthesis enzyme, is imprinted in mouse placenta. Proceedings of the National Academy of Sciences of the United States of America 100(8):4622−4627. https://doi.org/10.1073/pnas.0230424100

Van Pilsum, J. F., Stephens, G. C., and Taylor, D. 1972. Distribution of creatine, guanidinoacetate and the enzymes for their biosynthesis in the animal kingdom. Implications for phylogeny. Biochemical Journal 126:325−345. https://doi.org/10.1042/bj1260325

Yaffe, D. and Saxel, O. 1977. A myogenic cell line with altered serum requirements for differentiation a myogenic cell line with altered serum requirements for differentiation. Differentiation 7(3):159–166. https://doi.org/10.1111/j.1432-0436.1977.tb01507.x
Published
2018-11-30
How to Cite
Zhloba, A., Subbotina, T., Prikhodko, S., Khudiakov, A., Smolina, N., & Kostareva, A. (2018). Homoarginine and ornithine production during C2C12 myogenic differentiation. Biological Communications, 63(3), 174–179. https://doi.org/10.21638/spbu03.2018.303
Section
Full communication