Activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase does not respond to ubiquinone uptake in cultured cells (original) (raw)

Abstract

The cellular content of ubiquinone was increased approx. 10-fold by incubation of neuroblastoma cells in medium containing exogenous ubiquinone. Under these conditions the activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, assayed after preincubation of cell homogenates with or without fluoride, was not suppressed. Similar results were obtained with human skin fibroblast cultures to which free ubiquinone or low-density lipoprotein-ubiquinone complex had been added. Consistent with the lack of suppression of HMG-CoA reductase, the rate of incorporation of [1-14C] acetate into ubiquinone was not diminished in cells exposed to exogenous ubiquinone. Measurements of [3H]mevalonolactone incorporation into cellular ubiquinones indicated that exogenous ubiquinone did not affect ubiquinone synthesis at a point in the pathway distal to the formation of mevalonate. The results suggest that cultured mammalian cells lack an end-product 'feedback' mechanism for regulation of HMG-CoA reductase in response to ubiquinone uptake.

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Selected References

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  1. Adair W. L., Jr, Brennan S. L. The role of N-6-isopentenyl adenine in tumor cell growth. Biochem Biophys Res Commun. 1986 May 29;137(1):208–214. doi: 10.1016/0006-291x(86)91197-6. [DOI] [PubMed] [Google Scholar]
  2. Berndt J., Hegardt F. G., Bové J., Gaumert R., Still J., Cardó M. T. Activation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in vitro. Hoppe Seylers Z Physiol Chem. 1976 Sep;357(9):1277–1282. doi: 10.1515/bchm2.1976.357.2.1277. [DOI] [PubMed] [Google Scholar]
  3. Breslow J. L., Lothrop D. A., Spaulding D. R., Kandutsch A. A. Cholesterol, 7-ketocholesterol and 25-hydroxycholesterol uptake studies and effect on 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in human fibroblasts. Biochim Biophys Acta. 1975 Jul 22;398(1):10–17. doi: 10.1016/0005-2760(75)90165-4. [DOI] [PubMed] [Google Scholar]
  4. Brown M. S., Dana S. E., Goldstein J. L. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem. 1974 Feb 10;249(3):789–796. [PubMed] [Google Scholar]
  5. Brown M. S., Goldstein J. L., Dietschy J. M. Active and inactive forms of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the liver of the rat. Comparison with the rate of cholesterol synthesis in different physiological states. J Biol Chem. 1979 Jun 25;254(12):5144–5149. [PubMed] [Google Scholar]
  6. Brown M. S., Goldstein J. L. Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth. J Lipid Res. 1980 Jul;21(5):505–517. [PubMed] [Google Scholar]
  7. Brown M. S., Goldstein J. L. Suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and inhibition of growth of human fibroblasts by 7-ketocholesterol. J Biol Chem. 1974 Nov 25;249(22):7306–7314. [PubMed] [Google Scholar]
  8. Chen H. W., Heiniger H. J., Kandutsch A. A. Relationship between sterol synthesis and DNA synthesis in phytohemagglutinin-stimulated mouse lymphocytes. Proc Natl Acad Sci U S A. 1975 May;72(5):1950–1954. doi: 10.1073/pnas.72.5.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chin D. J., Luskey K. L., Faust J. R., MacDonald R. J., Brown M. S., Goldstein J. L. Molecular cloning of 3-hydroxy-3-methylglutaryl coenzyme a reductase and evidence for regulation of its mRNA. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7704–7708. doi: 10.1073/pnas.79.24.7704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crane F. L. Hydroquinone dehydrogenases. Annu Rev Biochem. 1977;46:439–469. doi: 10.1146/annurev.bi.46.070177.002255. [DOI] [PubMed] [Google Scholar]
  11. DULBECCO R., VOGT M. Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med. 1954 Feb;99(2):167–182. doi: 10.1084/jem.99.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fairbanks K. P., Witte L. D., Goodman D. S. Relationship between mevalonate and mitogenesis in human fibroblasts stimulated with platelet-derived growth factor. J Biol Chem. 1984 Feb 10;259(3):1546–1551. [PubMed] [Google Scholar]
  13. Faust J. R., Brown M. S., Goldstein J. L. Synthesis of delta 2-isopentenyl tRNA from mevalonate in cultured human fibroblasts. J Biol Chem. 1980 Jul 25;255(14):6546–6548. [PubMed] [Google Scholar]
  14. Faust J. R., Goldstein J. L., Brown M. S. Synthesis of ubiquinone and cholesterol in human fibroblasts: regulation of a branched pathway. Arch Biochem Biophys. 1979 Jan;192(1):86–99. doi: 10.1016/0003-9861(79)90074-2. [DOI] [PubMed] [Google Scholar]
  15. Folkers K., Wolaniuk J., Simonsen R., Morishita M., Vadhanavikit S. Biochemical rationale and the cardiac response of patients with muscle disease to therapy with coenzyme Q10. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4513–4516. doi: 10.1073/pnas.82.13.4513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gibbons G. F., Pullinger C. R., Chen H. W., Cavenee W. K., Kandutsch A. A. Regulation of cholesterol biosynthesis in cultured cells by probable natural precursor sterols. J Biol Chem. 1980 Jan 25;255(2):395–400. [PubMed] [Google Scholar]
  17. Gold P. H., Olson R. E. Studies on coenzyme Q. The biosynthesis of coenzyme Q9 in rat tissue slices. J Biol Chem. 1966 Aug 10;241(15):3507–3516. [PubMed] [Google Scholar]
  18. Goldstein J. L., Brown M. S. The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem. 1977;46:897–930. doi: 10.1146/annurev.bi.46.070177.004341. [DOI] [PubMed] [Google Scholar]
  19. Gough D. P., Hemming F. W. The characterization and stereochemistry of biosynthesis of dolichols in rat liver. Biochem J. 1970 Jun;118(1):163–166. doi: 10.1042/bj1180163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hall R. H. N6-(delta 2-isopentenyl)adenosine: chemical reactions, biosynthesis, metabolism, and significance to the structure and function of tRNA. Prog Nucleic Acid Res Mol Biol. 1970;10:57–86. doi: 10.1016/s0079-6603(08)60561-9. [DOI] [PubMed] [Google Scholar]
  22. James M. J., Kandutsch A. A. Inter-relationships between dolichol and sterol synthesis in mammalian cell cultures. J Biol Chem. 1979 Sep 10;254(17):8442–8446. [PubMed] [Google Scholar]
  23. James M. J., Kandutsch A. A. Regulation of hepatic dolichol synthesis by beta-hydroxy-beta-methylglutaryl coenzyme A reductase. J Biol Chem. 1980 Sep 25;255(18):8618–8622. [PubMed] [Google Scholar]
  24. Kandutsch A. A., Chen H. W., Heiniger H. J. Biological activity of some oxygenated sterols. Science. 1978 Aug 11;201(4355):498–501. doi: 10.1126/science.663671. [DOI] [PubMed] [Google Scholar]
  25. Kandutsch A. A., Chen H. W. Inhibition of sterol synthesis in cultured mouse cells by 7alpha-hydroxycholesterol, 7beta-hydroxycholesterol, and 7-ketocholesterol. J Biol Chem. 1973 Dec 25;248(24):8408–8417. [PubMed] [Google Scholar]
  26. Krieger M., McPhaul M. J., Goldstein J. L., Brown M. S. Replacement of neutral lipids of low density lipoprotein with esters of long chain unsaturated fatty acids. J Biol Chem. 1979 May 25;254(10):3845–3853. [PubMed] [Google Scholar]
  27. Krishnaiah K. V., Ramasarma T. Regulation of hepatic cholesterolgenesis by ubiquinone. Biochim Biophys Acta. 1970 Mar 10;202(2):332–342. doi: 10.1016/0005-2760(70)90195-5. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Liscum L., Luskey K. L., Chin D. J., Ho Y. K., Goldstein J. L., Brown M. S. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its mRNA in rat liver as studied with a monoclonal antibody and a cDNA probe. J Biol Chem. 1983 Jul 10;258(13):8450–8455. [PubMed] [Google Scholar]
  30. Littarru G. P., Jones D., Scholler J., Folkers K. Deficiency of coenzyme Q9 in mice having hereditary muscular dystrophy. Biochem Biophys Res Commun. 1970 Dec 9;41(5):1306–1313. doi: 10.1016/0006-291x(70)90231-7. [DOI] [PubMed] [Google Scholar]
  31. Mabuchi H., Haba T., Tatami R., Miyamoto S., Sakai Y., Wakasugi T., Watanabe A., Koizumi J., Takeda R. Effect of an inhibitor of 3-hydroxy-3-methyglutaryl coenzyme A reductase on serum lipoproteins and ubiquinone-10-levels in patients with familial hypercholesterolemia. N Engl J Med. 1981 Aug 27;305(9):478–482. doi: 10.1056/NEJM198108273050902. [DOI] [PubMed] [Google Scholar]
  32. Maltese W. A., Aprille J. R. Relation of mevalonate synthesis to mitochondrial ubiquinone content and respiratory function in cultured neuroblastoma cells. J Biol Chem. 1985 Sep 25;260(21):11524–11529. [PubMed] [Google Scholar]
  33. Maltese W. A., Reitz B. A., Volpe J. J. Changes in sterol biosynthesis accompanying cessation of glial cell growth in serum-free medium. Biochem J. 1980 Nov 15;192(2):709–717. doi: 10.1042/bj1920709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Maltese W. A., Sheridan K. M. Differentiation of neuroblastoma cells induced by an inhibitor of mevalonate synthesis: relation of neurite outgrowth and acetylcholinesterase activity to changes in cell proliferation and blocked isoprenoid synthesis. J Cell Physiol. 1985 Dec;125(3):540–558. doi: 10.1002/jcp.1041250326. [DOI] [PubMed] [Google Scholar]
  35. Martin H. G., Thorne K. J. Synthesis of radioactive dolichol from (4S-3H)mevalonate in the regenerating rat liver. Biochem J. 1974 Feb;138(2):277–280. doi: 10.1042/bj1380277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Mills J. T., Adamany A. M. Impairment of dolichyl saccharide synthesis and dolichol-mediated glycoprotein assembly in the aortic smooth muscle cell in culture by inhibitors of cholesterol biosynthesis. J Biol Chem. 1978 Aug 10;253(15):5270–5273. [PubMed] [Google Scholar]
  37. Nambudiri A. M., Ranganathan S., Rudney H. The role of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in the regulation of ubiquinone synthesis in human fibroblasts. J Biol Chem. 1980 Jun 25;255(12):5894–5899. [PubMed] [Google Scholar]
  38. Nordstrom J. L., Rodwell V. W., Mitschelen J. J. Interconversion of active and inactive forms of rat liver hydroxymethylglutaryl-CoA reductase. J Biol Chem. 1977 Dec 25;252(24):8924–8934. [PubMed] [Google Scholar]
  39. Ogasahara S., Yorifuji S., Nishikawa Y., Takahashi M., Wada K., Hazama T., Nakamura Y., Hashimoto S., Kono N., Tarui S. Improvement of abnormal pyruvate metabolism and cardiac conduction defect with coenzyme Q10 in Kearns-Sayre syndrome. Neurology. 1985 Mar;35(3):372–377. doi: 10.1212/wnl.35.3.372. [DOI] [PubMed] [Google Scholar]
  40. Peffley D., Sinensky M. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase synthesis by a non-sterol mevalonate-derived product in Mev-1 cells. Apparent translational control. J Biol Chem. 1985 Aug 25;260(18):9949–9952. [PubMed] [Google Scholar]
  41. Quesney-Huneeus V., Galick H. A., Siperstein M. D., Erickson S. K., Spencer T. A., Nelson J. A. The dual role of mevalonate in the cell cycle. J Biol Chem. 1983 Jan 10;258(1):378–385. [PubMed] [Google Scholar]
  42. Ranganathan S., Nambudiri A. M., Rudney H. The regulation of ubiquinone synthesis in fibroblasts: the effect of modulators of beta-hydroxy-beta-methylglutaryl-coenzyme A reductase activity. Arch Biochem Biophys. 1981 Sep;210(2):592–597. doi: 10.1016/0003-9861(81)90225-3. [DOI] [PubMed] [Google Scholar]
  43. Ranganathan S., Ramasarma T. The regulation of the biosynthesis of ubiquinone in the rat. Biochem J. 1975 Apr;148(1):35–39. doi: 10.1042/bj1480035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Rodwell V. W., Nordstrom J. L., Mitschelen J. J. Regulation of HMG-CoA reductase. Adv Lipid Res. 1976;14:1–74. doi: 10.1016/b978-0-12-024914-5.50008-5. [DOI] [PubMed] [Google Scholar]
  45. SIPERSTEIN M. D., FAGAN V. M. DELETION OF THE CHOLESTEROL-NEGATIVE FEEDBACK SYSTEM IN LIVER TUMORS. Cancer Res. 1964 Aug;24:1108–1115. [PubMed] [Google Scholar]
  46. Sabine J. R., Abraham S., Chaikoff I. L. Control of lipid metabolism in hepatomas: insensitivity of rate of fatty acid and cholesterol synthesis by mouse hepatoma BW7756 to fasting and to feedback control. Cancer Res. 1967 Apr;27(4):793–799. [PubMed] [Google Scholar]
  47. Saucier S. E., Kandutsch A. A. Inactive 3-hydroxy-3-methylglutaryl-coenzyme A reductase in broken cell preparations of various mammalian tissues and cell cultures. Biochim Biophys Acta. 1979 Mar 29;572(3):541–556. doi: 10.1016/0005-2760(79)90162-0. [DOI] [PubMed] [Google Scholar]
  48. Schmidt R. A., Glomset J. A., Wight T. N., Habenicht A. J., Ross R. A study of the Influence of mevalonic acid and its metabolites on the morphology of swiss 3T3 cells. J Cell Biol. 1982 Oct;95(1):144–153. doi: 10.1083/jcb.95.1.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Schmidt R. A., Schneider C. J., Glomset J. A. Evidence for post-translational incorporation of a product of mevalonic acid into Swiss 3T3 cell proteins. J Biol Chem. 1984 Aug 25;259(16):10175–10180. [PubMed] [Google Scholar]
  50. Schroepfer G. J., Jr Sterol biosynthesis. Annu Rev Biochem. 1981;50:585–621. doi: 10.1146/annurev.bi.50.070181.003101. [DOI] [PubMed] [Google Scholar]
  51. Sinensky M., Logel J. Defective macromolecule biosynthesis and cell-cycle progression in a mammalian cell starved for mevalonate. Proc Natl Acad Sci U S A. 1985 May;82(10):3257–3261. doi: 10.1073/pnas.82.10.3257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Singer T. P. Determination of the activity of succinate, NADH, choline, and alpha-glycerophosphate dehydrogenases. Methods Biochem Anal. 1974;22:123–175. doi: 10.1002/9780470110423.ch3. [DOI] [PubMed] [Google Scholar]
  53. Taylor F. R., Saucier S. E., Shown E. P., Parish E. J., Kandutsch A. A. Correlation between oxysterol binding to a cytosolic binding protein and potency in the repression of hydroxymethylglutaryl coenzyme A reductase. J Biol Chem. 1984 Oct 25;259(20):12382–12387. [PubMed] [Google Scholar]
  54. Trumpower B. L. New concepts on the role of ubiquinone in the mitochondrial respiratory chain. J Bioenerg Biomembr. 1981 Apr;13(1-2):1–24. doi: 10.1007/BF00744743. [DOI] [PubMed] [Google Scholar]
  55. Volpe J. J., Hennessy S. W. Cholesterol biosynthesis and 3-hydroxy-3-methyl-glutaryl coenzyme A reductase in cultured glial and neuronal cells. Regulation by lipoprotein and by certain free sterols. Biochim Biophys Acta. 1977 Mar 25;486(3):408–420. doi: 10.1016/0005-2760(77)90090-x. [DOI] [PubMed] [Google Scholar]
  56. Watson J. A., Havel C. M., Lobos D. V., Baker F. C., Morrow C. J. Isoprenoid synthesis in isolated embryonic Drosophila cells. Sterol-independent regulatory signal molecule is distal to isopentenyl 1-pyrophosphates. J Biol Chem. 1985 Nov 15;260(26):14083–14091. [PubMed] [Google Scholar]
  57. Weinstein J. D., Branchaud R., Beale S. I., Bement W. J., Sinclair P. R. Biosynthesis of the farnesyl moiety of heme a from exogenous mevalonic acid by cultured chick liver cells. Arch Biochem Biophys. 1986 Feb 15;245(1):44–50. doi: 10.1016/0003-9861(86)90188-8. [DOI] [PubMed] [Google Scholar]