Abstract
Experiments designed to test the hypothesis that intracellular creatine level regulates the synthesis of muscle specific proteins have failed to demonstrate any creatine regulatory effect. Manipulation of the extracellular creatine in culture medium over a 5,700-fold range (1.3- 7.4 mM) was successful in altering intracellular total creatine by only a factor of 20 (1.4-42 mg creatine/mg protein), an indication that muscle cells are able to regulate intracellular creatine levels over a wide range of external creatine concentrations. Alterations of cell creatine had no effect on either total protein synthesis or synthesis of myosin heavy chain. Methods were perfected to measure total creatine, and incorporation of [3H]leucine into total protein and purified myosin heavy chain from the same culture dish to avoid the possibility of variation between dishes. The creatine analog 1- carboxymethyl-2-iminohexahydropyrimidine (CMIP) previously reported to stimulate myosin synthesis in culture was found to depress creatine accumulation by cells and depressed total protein synthesis and synthesis of myosin heavy chain. This inhibitory action of CMIP is consistent with the reported competitive inhibition of creatine kinase and presumed interference with energy metabolism.
Full Text
The Full Text of this article is available as a PDF (332.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- CONN R. B., Jr Fluorimetric determination of creatine. Clin Chem. 1960 Dec;6:537–548. [PubMed] [Google Scholar]
- Ingwall J. S., Morales M. F., Stockdale F. E. Creatine and the control of myosin synthesis in differentiating skeletal muscle. Proc Natl Acad Sci U S A. 1972 Aug;69(8):2250–2253. doi: 10.1073/pnas.69.8.2250. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ingwall J. S., Weiner C. D., Morales M. F., Davis E., Stockdale F. E. Specificity of creatine in the control of muscle protein synthesis. J Cell Biol. 1974 Jul;62(1):145–151. doi: 10.1083/jcb.62.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- McLaughlin A. C., Cohn M., Kenyon G. L. Specificity of creatine kinase for guanidino substrates. Kinetic and proton nuclear magnetic relaxation rate studies. J Biol Chem. 1972 Jul 10;247(13):4382–4388. [PubMed] [Google Scholar]
- O'Neill M. C., Stockdale F. E. A kinetic analysis of myogenesis in vitro. J Cell Biol. 1972 Jan;52(1):52–65. doi: 10.1083/jcb.52.1.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paterson B., Strohman R. C. Myosin structure as revealed by simultaneous electrophoresis of heavy and light subunits. Biochemistry. 1970 Oct 13;9(21):4094–4105. doi: 10.1021/bi00823a010. [DOI] [PubMed] [Google Scholar]
- Tonomura Y., Appel P., Morales M. On the molecular weight of myosin. II. Biochemistry. 1966 Feb;5(2):515–521. doi: 10.1021/bi00866a017. [DOI] [PubMed] [Google Scholar]
- Wilson B. W., Stinnett H. O., Fry D. M., Nieberg P. S. Growth and metabolism of chick embryo muscle cultures. Inhibition with malathion and other organophosphorus compounds. Arch Environ Health. 1973 Feb;26(2):93–99. doi: 10.1080/00039896.1973.10666232. [DOI] [PubMed] [Google Scholar]
- Wilson B. W., Stinnett H. O. Growth and respiration of monolayer cell cultures of chick embryo heart and skeletal muscle: action of malathion and malaoxon. Proc Soc Exp Biol Med. 1969 Jan;130(1):30–34. doi: 10.3181/00379727-130-33481. [DOI] [PubMed] [Google Scholar]