Abstract
The polypeptide growth factors, nerve growth factor, epidermal growth factor, and platelet-derived growth factor, as well as insulin do not induce ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) unless a minimal concentration of an ornithine decarboxylase-inducing amino acid, such as asparagine, is present in the medium. The effects of the growth factors were studied in appropriately responsive cell lines: pheochromocytoma (PC12) cells for nerve and epidermal growth factors, fibroblasts (NIH 3T3) for platelet-derived growth factor, and fibroblasts and hepatoma (KRC-7) cells for insulin. The nonmetabolizable amino acid analog alpha-aminoisobutyric acid can replace asparagine, indicating that the covalent modification of the inducing amino acid is not necessary for the induction of ornithine decarboxylase by these growth factors. For the same intracellular concentration of the inducing amino acid, the presence of the growth factors induces higher levels of ornithine decarboxylase. The evidence indicates that these growth factors do not induce ornithine decarboxylase by raising the intracellular concentration of amino acids but rather act synergistically with the inducing amino acid. Evidence is provided that the induction of polyamine-dependent growth by these growth factors is mediated by amino acids. The relationship of these results to the A and N amino acid transport systems and to the Na+ influxes in relation to growth is discussed.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Carpenter G., Cohen S. Epidermal growth factor. Annu Rev Biochem. 1979;48:193–216. doi: 10.1146/annurev.bi.48.070179.001205. [DOI] [PubMed] [Google Scholar]
- Chen K. Y., Canellakis E. S. Enzyme regulation in neuroblastoma cells in a salts/glucose medium: induction of ornithine decarboxylase by asparagine and glutamine. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3791–3795. doi: 10.1073/pnas.74.9.3791. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen K. Y., Liu A. Y. Differences in the mode of regulation of ornithine decarboxylase and tyrosine aminotransferase in H-35 rat hepatoma cells shown by varying the medium composition. Biochim Biophys Acta. 1983 Jan 25;755(2):244–252. doi: 10.1016/0304-4165(83)90210-6. [DOI] [PubMed] [Google Scholar]
- Chideckel E. W., Edwards D. Non-metabolizable amino acids are potent stimulators of hepatic and renal ornithine decarboxylase activity. Biochem J. 1983 Feb 15;210(2):617–619. doi: 10.1042/bj2100617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Costa M. The regulation of ornithine decarboxylase activity in intact normal and transformed cells maintained with a minimal salts/glucose medium. Life Sci. 1979 Dec 10;25(24-25):2113–2124. doi: 10.1016/0024-3205(79)90205-4. [DOI] [PubMed] [Google Scholar]
- DisPasquale A., White D., McGuire J. Epidermal growth factor stimulates putrescine transport and ornithine decarboxylase activity in cultivated human fibroblasts. Exp Cell Res. 1978 Oct 15;116(2):317–323. doi: 10.1016/0014-4827(78)90454-8. [DOI] [PubMed] [Google Scholar]
- Guroff G., Dickens G., End D. The induction of ornithine decarboxylase by nerve growth factor and epidermal growth factor in PC12 cells. J Neurochem. 1981 Aug;37(2):342–349. doi: 10.1111/j.1471-4159.1981.tb00461.x. [DOI] [PubMed] [Google Scholar]
- Haselbacher G. K., Humbel R. E. Stimulation of ornithine decarboxylase activity in chick fibroblasts by non-suppressible insulin-like activity (NSILA), insulin and serum. J Cell Physiol. 1976 Jun;88(2):239–245. doi: 10.1002/jcp.1040880213. [DOI] [PubMed] [Google Scholar]
- Hatanaka H., Otten U., Thoenen H. Nerve growth factor-mediated selective induction of ornithine decarboxylase in rat pheochromocytoma; a cyclic AMP-independent process. FEBS Lett. 1978 Aug 15;92(2):313–316. doi: 10.1016/0014-5793(78)80777-7. [DOI] [PubMed] [Google Scholar]
- Heby O. Role of polyamines in the control of cell proliferation and differentiation. Differentiation. 1981;19(1):1–20. doi: 10.1111/j.1432-0436.1981.tb01123.x. [DOI] [PubMed] [Google Scholar]
- Kilberg M. S., Handlogten M. E., Christensen H. N. Characteristics of an amino acid transport system in rat liver for glutamine, asparagine, histidine, and closely related analogs. J Biol Chem. 1980 May 10;255(9):4011–4019. [PubMed] [Google Scholar]
- Moolenaar W. H., Yarden Y., de Laat S. W., Schlessinger J. Epidermal growth factor induces electrically silent Na+ influx in human fibroblasts. J Biol Chem. 1982 Jul 25;257(14):8502–8506. [PubMed] [Google Scholar]
- Owen A. J., 3rd, Geyer R. P., Antoniades H. N. Human platelet-derived growth factor stimulates amino acid transport and protein synthesis by human diploid fibroblasts in plasma-free media. Proc Natl Acad Sci U S A. 1982 May;79(10):3203–3207. doi: 10.1073/pnas.79.10.3203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pegg A. E., McCann P. P. Polyamine metabolism and function. Am J Physiol. 1982 Nov;243(5):C212–C221. doi: 10.1152/ajpcell.1982.243.5.C212. [DOI] [PubMed] [Google Scholar]
- Pledger W. J., Stiles C. D., Antoniades H. N., Scher C. D. Induction of DNA synthesis in BALB/c 3T3 cells by serum components: reevaluation of the commitment process. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4481–4485. doi: 10.1073/pnas.74.10.4481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Potter V. R., Evanson T. R., Gayda D. P., Gurr J. A. Cultured hepatoma cells for the study of enzyme regulation: induction of ornithine decarboxylase by insulin and asparagine. In Vitro. 1984 Sep;20(9):723–731. doi: 10.1007/BF02618878. [DOI] [PubMed] [Google Scholar]
- Rinehart C. A., Jr, Viceps-Madore D., Fong W. F., Ortiz J. G., Canellakis E. S. The effect of transport system A and N amino acids and of nerve and epidermal growth factors on the induction of ornithine decarboxylase activity. J Cell Physiol. 1985 Jun;123(3):435–441. doi: 10.1002/jcp.1041230321. [DOI] [PubMed] [Google Scholar]
- Skaper S. D., Varon S. Maintenance by nerve growth factor of the intracellular sodium environment in spinal sensory and sympathetic ganglionic cells. Brain Res. 1980 Sep 22;197(2):379–389. doi: 10.1016/0006-8993(80)91123-3. [DOI] [PubMed] [Google Scholar]
- Stastny M., Cohen S. Epidermal growth factor. IV. The induction of ornithine decarboxylase. Biochim Biophys Acta. 1970 Apr 15;204(2):578–589. [PubMed] [Google Scholar]
- Varon S., Skaper S. D. Short-latency ionic effects of nerve growth factor deprivation and readministration on ganglionic cells. J Supramol Struct. 1980;13(3):329–337. doi: 10.1002/jss.400130306. [DOI] [PubMed] [Google Scholar]
- Viceps-Madore D., Chen K. Y., Tsou H. R., Canellakis E. S. Studies on the role of protein synthesis and of sodium on the regulation of ornithine decarboxylase activity. Biochim Biophys Acta. 1982 Aug 6;717(2):305–315. doi: 10.1016/0304-4165(82)90184-2. [DOI] [PubMed] [Google Scholar]
- Villereal M. L. Sodium fluxes in human fibroblasts: effect of serum, Ca+2, and amiloride. J Cell Physiol. 1981 Jun;107(3):359–369. doi: 10.1002/jcp.1041070307. [DOI] [PubMed] [Google Scholar]
- Yankner B. A., Shooter E. M. The biology and mechanism of action of nerve growth factor. Annu Rev Biochem. 1982;51:845–868. doi: 10.1146/annurev.bi.51.070182.004213. [DOI] [PubMed] [Google Scholar]