Abstract
The regulation of creatine phosphokinase (CPK) expression by polypeptide growth factors has been examined in the clonal mouse muscle BC3H1 cell line. After arrest of cell growth by exposure to low concentrations of serum, BC3H1 cells accumulate high levels of muscle- specific proteins including CPK. The induction of this enzyme is reversible in the presence of high concentrations of fetal calf serum, which cause quiescent, differentiated cells to reenter the cell cycle. Under these conditions, the rate of CPK synthesis is drastically reduced. We show in the present communication that either pituitary- derived fibroblast growth factor (FGF) or brain-derived FGF are as effective as serum in repressing the synthesis of CPK when added to quiescent, differentiated cells. The decrease in the rate of synthesis of CPK occurs within 22 h after the addition of pituitary FGF to the cells. Pituitary FGF had very little effect, if any, on the rate CPK degradation. The overall rate of protein synthesis and the pattern of synthesis of the major polypeptides made by these cells was not altered by the addition of FGF. Although pituitary FGF was mitogenic for BC3H1 cells, the rate of cell growth was not absolutely correlated with the extent of repression of CPK. Brain-derived FGF fully repressed CPK induction under conditions where it showed no significant mitogenic activity. These results show that the expression of a muscle-specific protein, CPK, can be controlled by a single defined polypeptide growth factor in fully differentiated cultures, and that initiation of cell division is not required for their regulation to take place.
Full Text
The Full Text of this article is available as a PDF (1.6 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Borrelli E., Hen R., Chambon P. Adenovirus-2 E1A products repress enhancer-induced stimulation of transcription. Nature. 1984 Dec 13;312(5995):608–612. doi: 10.1038/312608a0. [DOI] [PubMed] [Google Scholar]
- Böhlen P., Baird A., Esch F., Ling N., Gospodarowicz D. Isolation and partial molecular characterization of pituitary fibroblast growth factor. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5364–5368. doi: 10.1073/pnas.81.17.5364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Devlin B. H., Konigsberg I. R. Reentry into the cell cycle of differentiated skeletal myocytes. Dev Biol. 1983 Jan;95(1):175–192. doi: 10.1016/0012-1606(83)90016-7. [DOI] [PubMed] [Google Scholar]
- Dollenmeier P., Turner D. C., Eppenberger H. M. Proliferation and differentiation of chick skeletal muscle cells cultured in a chemically defined medium. Exp Cell Res. 1981 Sep;135(1):47–61. doi: 10.1016/0014-4827(81)90298-6. [DOI] [PubMed] [Google Scholar]
- Evinger-Hodges M. J., Ewton D. Z., Seifert S. C., Florini J. R. Inhibition of myoblast differentiation in vitro by a protein isolated from liver cell medium. J Cell Biol. 1982 May;93(2):395–401. doi: 10.1083/jcb.93.2.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gospodarowicz D., Hirabayashi K., Giguère L., Tauber J. P. Factors controlling the proliferative rate, final cell density, and life span of bovine vascular smooth muscle cells in culture. J Cell Biol. 1981 Jun;89(3):568–578. doi: 10.1083/jcb.89.3.568. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gospodarowicz D. Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth. Nature. 1974 May 10;249(453):123–127. doi: 10.1038/249123a0. [DOI] [PubMed] [Google Scholar]
- Gospodarowicz D., Weseman J., Moran J. S., Lindstrom J. Effect of fibroblast growth factor on the division and fusion of bovine myoblasts. J Cell Biol. 1976 Aug;70(2 Pt 1):395–405. doi: 10.1083/jcb.70.2.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Konigsberg I. R., Sollmann P. A., Mixter L. O. The duration of the terminal G1 of fusing myoblasts. Dev Biol. 1978 Mar;63(1):11–26. doi: 10.1016/0012-1606(78)90109-4. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Linkhart T. A., Clegg C. H., Hauschika S. D. Myogenic differentiation in permanent clonal mouse myoblast cell lines: regulation by macromolecular growth factors in the culture medium. Dev Biol. 1981 Aug;86(1):19–30. doi: 10.1016/0012-1606(81)90311-0. [DOI] [PubMed] [Google Scholar]
- Linkhart T. A., Clegg C. H., Hauschka S. D. Control of mouse myoblast commitment to terminal differentiation by mitogens. J Supramol Struct. 1980;14(4):483–498. doi: 10.1002/jss.400140407. [DOI] [PubMed] [Google Scholar]
- Medford R. M., Nguyen H. T., Nadal-Ginard B. Transcriptional and cell cycle-mediated regulation of myosin heavy chain gene expression during muscle cell differentiation. J Biol Chem. 1983 Sep 25;258(18):11063–11073. [PubMed] [Google Scholar]
- Merlie J. P., Buckingham M. E., Whalen R. G. Molecular aspects of myogenesis. Curr Top Dev Biol. 1977;11:61–114. doi: 10.1016/s0070-2153(08)60743-7. [DOI] [PubMed] [Google Scholar]
- Munson R., Jr, Caldwell K. L., Glaser L. Multiple controls for the synthesis of muscle-specific proteins in BC3H1 cells. J Cell Biol. 1982 Feb;92(2):350–356. doi: 10.1083/jcb.92.2.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nadal-Ginard B. Commitment, fusion and biochemical differentiation of a myogenic cell line in the absence of DNA synthesis. Cell. 1978 Nov;15(3):855–864. doi: 10.1016/0092-8674(78)90270-2. [DOI] [PubMed] [Google Scholar]
- Nguyen H. T., Medford R. M., Nadal-Ginard B. Reversibility of muscle differentiation in the absence of commitment: analysis of a myogenic cell line temperature-sensitive for commitment. Cell. 1983 Aug;34(1):281–293. doi: 10.1016/0092-8674(83)90159-9. [DOI] [PubMed] [Google Scholar]
- Olson E. N., Caldwell K. L., Gordon J. I., Glaser L. Regulation of creatine phosphokinase expression during differentiation of BC3H1 cells. J Biol Chem. 1983 Feb 25;258(4):2644–2652. [PubMed] [Google Scholar]
- Olson E. N., Glaser L., Merlie J. P., Lindstrom J. Expression of acetylcholine receptor alpha-subunit mRNA during differentiation of the BC3H1 muscle cell line. J Biol Chem. 1984 Mar 10;259(5):3330–3336. [PubMed] [Google Scholar]
- Olson E. N., Glaser L., Merlie J. P., Sebanne R., Lindstrom J. Regulation of surface expression of acetylcholine receptors in response to serum and cell growth in the BC3H1 muscle cell line. J Biol Chem. 1983 Nov 25;258(22):13946–13953. [PubMed] [Google Scholar]
- Olson E. N., Lathrop B. K., Glaser L. Purification and cell-free translation of a unique high molecular weight form of the brain isozyme of creatine phosphokinase from mouse. Biochem Biophys Res Commun. 1982 Sep 30;108(2):715–723. doi: 10.1016/0006-291x(82)90888-9. [DOI] [PubMed] [Google Scholar]
- Pardee A. B., Dubrow R., Hamlin J. L., Kletzien R. F. Animal cell cycle. Annu Rev Biochem. 1978;47:715–750. doi: 10.1146/annurev.bi.47.070178.003435. [DOI] [PubMed] [Google Scholar]
- Savage C. R., Jr, Cohen S. Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization. J Biol Chem. 1972 Dec 10;247(23):7609–7611. [PubMed] [Google Scholar]
- Schubert D., Harris A. J., Devine C. E., Heinemann S. Characterization of a unique muscle cell line. J Cell Biol. 1974 May;61(2):398–413. doi: 10.1083/jcb.61.2.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas K. A., Rios-Candelore M., Fitzpatrick S. Purification and characterization of acidic fibroblast growth factor from bovine brain. Proc Natl Acad Sci U S A. 1984 Jan;81(2):357–361. doi: 10.1073/pnas.81.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinstein R., Stemerman M. B., Maciag T. Hormonal requirements for growth of arterial smooth muscle cells in vitro: and endocrine approach to atherosclerosis. Science. 1981 May 15;212(4496):818–820. doi: 10.1126/science.7013068. [DOI] [PubMed] [Google Scholar]