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Effects of monensin on ATP levels and cell functions in rat liver and lung in vitro

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Summary

Effects of the proton-alkali cation-exchanging ionophore, monensin, on aspects of cellular metabolism and ionic exchanges have been studied in rat tissues in vitro. Incubation of liver slices at 38°C with 0.1 μm monensin induced timedependent vesiculation, initially in the Golgi region, reduction of ATP content and of protein synthesis. At 1 νm, monensin also reduced net, active movements of K+, Na+, Cl− and water in liver slices and inhibited state 3 respiration in isolated mitochondria. The respiratory inhibitor, amytal, similarly reduced ATP content and protein synthesis at concentrations lower than those inhibiting ion transport in slices. Low concentrations of monensin (0.1–1.0 μm) had similar effects on ATP and ion transport in slices of adult lung. By contrast, late-fetal liver and lung were much less sensitive to monensin; in these tissues, glycolysis sustained substantial levels of ATP. Monensin also induced vesiculation of the Golgi apparatus in fetal lung cells. It is concluded that by lowering ATP levels, monensin can markedly alter various metabolic activities in those cells which depend primarily on oxidative phosphorylation for their metabolic energy.

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References

  1. Blond, D.M., Whittam, R. 1964. The regulation of kidney respiration by sodium and potassium ions.Biochem. J. 92:158–167

    PubMed  Google Scholar 

  2. Chance, B., Williams, G.R. 1955. Respiratory enzymes in oxidative phosphorylation. III. The steady state.J. Biol. Chem. 217:409–427

    Google Scholar 

  3. Chander, A., Johnson, R.G., Reicherter, J., Fisher, A.B. 1986. Lung lamellar bodies maintain an acidic internal pH.J. Biol. Chem. 261:6126–6131

    PubMed  Google Scholar 

  4. Danielsen, E.M., Cowell, G.M., Poulsen, S.S. 1983. Biosynthesis of intestinal microvillar proteins. Role of the Golgi complex and microtubules.Biochem. J. 216:37–42

    PubMed  Google Scholar 

  5. Di Virgilio, F., Gomperts, B.D. 1983. Ionophore monensin induces Na+-dependent secretion from rabbit neutrophils.Biochim. Biophys. Acta 763:292–298

    PubMed  Google Scholar 

  6. Elshove, A., Rossum, G.D.V. van. 1963. Net movements of sodium and potassium, and their relation to respiration, in slices of rat liver in vitro.J. Physiol. (London) 168:531–553

    Google Scholar 

  7. Ennis, H.L., Sells, B.H. 1968. Breakdown and reformation of polysomes inEscherichia coli during inhibition of protein synthesis.Biochim. Biophys. Acta 161:503–508

    PubMed  Google Scholar 

  8. Estrada-O. S., Rightmire, B., Lardy, H.A. 1968. Antibiotics as tools for metabolic studies. XI. Specific inhibition of ion transport in mitochondria by the monensins.In: Antimicrobial Agents and Chemotherapy-1967. pp. 279–288. American Society for Microbiology

  9. Glickman, J., Croen, K., Kelly, S., Al-Awqati, Q. 1983. Golgi membranes contain an electrogenic H+ pump in parallel to a chloride conductance.J. Cell Biol. 97:1303–1308

    PubMed  Google Scholar 

  10. Giffing, L.G., Ray, P.M. 1985. Involvement of monovalent cations in Golgi secretion by plant cells.Eur. J. Cell Biol. 36:24–31

    Google Scholar 

  11. Hackenbrock, C.R. 1966. Ultrastructural bases for metabolically linked mechanical activity in mitochondria. I. Reversible ultrastructural changes with change in metabolic steady state in isolated liver mitochondria.J. Cell Biol. 30:269–297

    PubMed  Google Scholar 

  12. Höfer, M., Pressman, B.C. 1966. Stimulation of oxidative phosphorylation in mitochondria by potassium in the presence of valinomycin.Biochemistry 5:3919–3925

    Google Scholar 

  13. Kloppel, T.M., Brown, W.R., Reichen, J. 1986. Effects of monensin on vesicular transport pathways in the perfused rat liver.J. Cell Biochem. 32:235–245

    PubMed  Google Scholar 

  14. Lardy, H.A., Graven, S.N., Estrada-O, S. 1967. Specific induction and inhibition of cation and anion transport in mitochondria.Fed. Proc. Fed. Am. Soc. Exp. Biol. 26:1355–1360

    Google Scholar 

  15. Mariani, M.F., Schisselbauer, J.C., DeFeo, B., Rossum, G.D.V. van 1986. Effect of monensin on liver-cell function and ultrastructure.Fed. Proc. Fed. Am. Soc. Exp. Biol. 45:423

    Google Scholar 

  16. Mellman, I., Fuchs, R., Helenius, A. 1986. Acidification of the endocytic and exocytic pathways.Annu. Rev. Biochem. 55:663–700

    PubMed  Google Scholar 

  17. Montal, M., Chance, B., Lee, C.P. 1970. Ion transport and energy conservation in submitochondrial particles.J. Membrane Biol. 2:201–234

    Google Scholar 

  18. Morré, J.D., Morré, D.M., Mollenhauer, H.H., Reutter, W. 1987. Golgi apparatus cisternae of monensin-treated cells accumulate in the cytoplasm of liver slices.Eur. J. Cell Biol.43:235–242

    PubMed  Google Scholar 

  19. Munro, A.J., Jackson, R.J., Korner, A. 1964. Studies on the nature of polysomes.Biochem. J. 92:289–299

    PubMed  Google Scholar 

  20. Pressman, B.C., Harris, E.J., Jagger, W.S., Johnson, J.H. 1967. Antibiotic-mediated transport of alkali ions across lipid barriers.Proc. Natl. Acad. Sci. USA 58:1949–1956

    PubMed  Google Scholar 

  21. Pressman, B.C., Lardy, H.A. 1952. Influence of potassium and other alkali cations on respiration of mitochondria.J. Biol. Chem. 197:547–556

    PubMed  Google Scholar 

  22. Puttfarcken, P., Werling, L.L., Brown, S.R., Cote, T.E., Cox, B.M. 1986. Sodium regulation of agonist binding at opioid receptors. I. Effects of sodium replacement on binding at μ- and δ-type receptors in 7315c and NG108-15 cells and cell membranes.Mol. Pharmacol. 30:81–89

    PubMed  Google Scholar 

  23. Rossum, G.D.V. van. 1963. Net sodium and potassium movements in liver slices prepared from rats of different foetal and post-natal ages.Biochim. Biophys. Acta 74:1–14

    PubMed  Google Scholar 

  24. Rossum, G.D.V. van. 1972. The relation of sodium and potassium ion transport to the respiration and adenine nucleotide content of liver slices treated with inhibitors of respiration.Biochem. J. 129:427–438

    PubMed  Google Scholar 

  25. Rossum, G.D.V. van. 1976. Effects of oligomycin on energy metabolism and cation transport in slices of rat liver. Inhibition of oxidative phosphorylation as the primary action.Biochim. Biophys. Acta 423:111–121

    PubMed  Google Scholar 

  26. Rossum, G.D.V. van, Russo, M.A., Schisselbauer, J.C. 1987. Role of cytoplasmic vesicles in volume maintenance.In:Current Topics in Membranes and Transport. R. Gilles, A. Kleinzeller, and L. Bolis, editors. Vol. 30, pp. 45–74. Academic, New York

    Google Scholar 

  27. Russo, M.A., Galeotti, T., Rossum, G.D.V. van. 1976. The metabolism-dependent maintenance of cell volume and ultrastructure in slices of Morris hepatoma 3924A.Cancer Res. 36:4160–4174

    PubMed  Google Scholar 

  28. Russo, M.A., Rossum, G.D.V. van. 1986. The basis for the cellular damage induced by ethacrynic acid in liver slices in vitro. Comparison of structure and function.Lab. Invest. 54:695–707

    PubMed  Google Scholar 

  29. Russo, M.A., Rossum, G.D.V. van, Galeotti, T. 1977. Observations on the regulation of cell volumes and metabolic control in vitro: Changes in composition and ultrastructure of liver slices under conditions of varying metabolic and transporting activity.J. Membrane Biol. 31:267–299

    Google Scholar 

  30. Rustan, A.C., Nossen, J.O., Berg, T., Drevon, C.A. 1985. The effects of monensin on secretion of very-low-density lipoprotein and metabolism of asialofetuin by cultured rat hepatocytes.Biochem. J. 227:529–536

    PubMed  Google Scholar 

  31. Saermark, T., Flint, N., Evans, W.H. 1985. Hepatic endosome fractions contain an ATP-driven proton pump.Biochem. J. 225:51–58

    PubMed  Google Scholar 

  32. Suchard, S.J., Lattanzio, F.A., Rubin, R.W., Pressman, B.C. 1982. Stimulation of catecholamine secretion from cultured chromaffin cells by an ionophore-mediated rise in intracellular sodium.J. Cell Biol. 94:531–539

    PubMed  Google Scholar 

  33. Tartakoff, A.M. 1983. Perturbation of vesicular traffic with the carboxylic ionophore monensin.Cell 32:1026–1028

    PubMed  Google Scholar 

  34. Tartakoff, A.M., Vassalli, P. 1977. Plasma cell immunoglobulin secretion. Arrest is accompanied by alteration of the Golgi complex.J. Exp. Med. 146:1332–1345

    PubMed  Google Scholar 

  35. Tartakoff, A.M., Vassalli, P. 1978. Comparative studies of intracellular transport of secretory proteins.J. Cell. Biol. 79:694–707

    PubMed  Google Scholar 

  36. Uchida, N., Smilowitz, H., Tanzer, M.L. 1979. Monovalent ionophores inhibit secretion of procollagen and fibronectin from cultured human fibroblasts.Proc. Natl. Acad. Sci. USA 76:1868–1872

    PubMed  Google Scholar 

  37. Van Dyke, R.W., Hornick, C.R., Belcher, J., Scharschmidt, B.F., Havel, R.J. 1985. Identification and characterization of ATP-dependent proton transport by rat liver multivesicular bodies.J. Biol. Chem. 260:11021–11026

    PubMed  Google Scholar 

  38. Watson, E.L., Farnham, C.J., Friedman, J., Farnham, W. 1981. Effects of monensin on amylase release from mouse parotid acini.Am. J. Physiol. 240:C189-C192

    PubMed  Google Scholar 

  39. Zhang, F., Schneider, D.L. 1983. The bioenergetics of Golgi apparatus function: Evidence for an ATP-dependent proton pump.Biochem. Biophys. Res. Commun. 114:620–625

    PubMed  Google Scholar 

  40. Zoratti, M., Favaron, M., Pietrobon, D., Petronilli, V. 1984. Nigericin-induced transient changes in rat-liver mitochondria.Biochim. Biophys. Acta 767:231–239

    PubMed  Google Scholar 

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Author notes

  1. Maurizio F. Mariani

    Present address: Dipartimento di Medicina Sperimentale, Università “La Sapienza”, Viale Regina Elena, 324, 00161, Rome, Italy

Authors and Affiliations

  1. Department of Pharmacology, Temple University School of Medicine, 19140, Philadelphia, Pennsylvania

    Maurizio F. Mariani, Lucy Thomas, Brenda DeFeo & George D. V. van Rossum

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  1. Maurizio F. Mariani
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  2. Lucy Thomas
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  3. Brenda DeFeo
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  4. George D. V. van Rossum
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Mariani, M.F., Thomas, L., DeFeo, B. et al. Effects of monensin on ATP levels and cell functions in rat liver and lung in vitro. J. Membrain Biol. 108, 235–246 (1989). https://doi.org/10.1007/BF01871738

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  • DOI: https://doi.org/10.1007/BF01871738

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