1887

Abstract

One of the long-chain alkyl esters of AMP, adenosine 5′-hexadecylphosphate (AMPC16), exhibited a cytotoxic growth inhibitory effect on cells of various yeast strains. The growth inhibitory effect of AMPC16 on cells was observed only in medium containing Mg, which accelerated cellular uptake of the nucleotide analogue. In the presence of Mg, AMPC16 completely inhibited glucose-induced extracellular acidification by the intact cells and also interfered with activation of the plasma membrane ATPase, but did not directly inhibit the ATPase activity itself. AMPC16 treatment prevented cells from increasing their intracellular 1,2-diacylglycerol (DAG) level in response to glucose, whereas the inhibition of proton extrusion by the cells could be largely reversed by the coaddition of a membrane-permeable DAG analogue. The DAG analogue, a physiological activator of protein kinase C (PKC), was not protective against the inhibition of glucose-induced proton extrusion by staurosporine, which is capable of directly interfering with the action of PKC. These results implied that AMPC16 caused a Mg-dependent cytotoxic effect on cells by interfering with a phosphatidylinositol type of signal that mediates activation of the plasma membrane proton pump.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-146-2-377
2000-02-01
2019-10-20
Loading full text...

Full text loading...

/deliver/fulltext/micro/146/2/1460377a.html?itemId=/content/journal/micro/10.1099/00221287-146-2-377&mimeType=html&fmt=ahah

References

  1. Akeda, Y., Shibata, K., Ping, X., Tanaka, T. & Taniguchi, M. ( 1995; ). AKD-2A, B, C and D, new antibiotics from Streptomyces sp. OCU-42815: taxonomy, fermentation, isolation, structure elucidation and biological activity. J Antibiot 48, 363-368.[CrossRef]
    [Google Scholar]
  2. Baltch, A. L., Smith, R. P., Ritz, W. J. & Bopp, L. H. ( 1998; ). Comparison of inhibitory and bactericidal activities and postantibiotic effects of LY333328 and ampicillin used singly and in combination against vancomycin-resistant Enterococcus faecium. Antimicrob Agents Chemother 42, 2564-2568.
    [Google Scholar]
  3. Becher dos Passos, J., Vanhalewyn, M., Brandão, R. L., Castro, I. M., Nicoli, J. R. & Thevelein, J. M. ( 1992; ). Glucose-induced activation of plasma membrane H+-ATPase in mutants of the yeast Saccharomyces cerevisiae affected in cAMP metabolism, cAMP-dependent protein phosphorylation and the initiation of glycolysis. Biochim Biophys Acta 1136, 57-67.[CrossRef]
    [Google Scholar]
  4. Bradford, M. M. ( 1976; ). A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72, 248-254.[CrossRef]
    [Google Scholar]
  5. Brandão, R. L., de Magalhaes-Rocha, N. M., Alijo, R., Ramos, J. & Thevelein, J. M. ( 1994; ). Possible involvement of a phosphatidylinositol-type signaling pathway in glucose-induced activation of plasma membrane H+-ATPase and cellular proton extrusion in the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1223, 117-124.[CrossRef]
    [Google Scholar]
  6. Chang, A. & Slayman, C. W. ( 1991; ). Maturation of the yeast plasma membrane [H+]ATPase involves phosphorylation during intracellular transport. J Cell Biol 115, 289-295.[CrossRef]
    [Google Scholar]
  7. Coccetti, P., Tisi, R., Martegani, E., Sousa Teixeira, L., Brandão, R. L., Castro, I. M. & Thevelein, J. M. ( 1998; ). The PLC1 encoded phospholipase C in the yeast Saccharomyces cerevisiae is essential for glucose-induced phosphatidylinositol turnover and activation of plasma membrane H+-ATPase. Biochim Biophys Acta 1405, 147-154.[CrossRef]
    [Google Scholar]
  8. Haug, J. S., Goldner, C. M., Yazlovitskaya, E. M., Voziyan, P. A. & Melnykovych, G. ( 1994; ). Directed cell killing (apoptosis) in human lymphoblastoid cells incubated in the presence of farnesol: effect of phosphatidylcholine. Biochim Biophys Acta 1223, 133-140.[CrossRef]
    [Google Scholar]
  9. Herve, M., Debouzy, J. C., Borowski, E., Cybulska, B. & Gary-Bobo, C. M. ( 1989; ). The role of the carboxyl and amino groups of polyene macrolides in their interactions with sterols and their selective toxicity: a phosphorus-31 NMR study. Biochim Biophys Acta 980, 261-272.[CrossRef]
    [Google Scholar]
  10. Hynie, S. & Smrt, J. ( 1978; ). Effects of adenosine 5′-phosphate esters with lipid hydroxy compounds (adenosine nucleolipids) on the activity of enzymes of cyclic AMP system. FEBS Lett 94, 339-341.[CrossRef]
    [Google Scholar]
  11. Johnson, D. R., Knoll, L. J., Rowley, N. & Gordon, J. I. ( 1994; ). Genetic analysis of the role of Saccharomyces cerevisiae acyl-CoA synthetase genes in regulating protein N-myristoylation. J Biol Chem 269, 18037-18046.
    [Google Scholar]
  12. Knoll, L. J., Johnson, D. R. & Gordon, J. I. ( 1995; ). Complementation of Saccharomyces cerevisiae strains containing fatty acid activation gene (FAA) deletions with a mammalian acyl-CoA synthetase. J Biol Chem 270, 10861-10867.[CrossRef]
    [Google Scholar]
  13. Kohner, P. C., Patel, R., Uhl, J. R., Garin, K. M., Hopkins, M. K., Wegener, L. T. & Cockerill, F. R.III ( 1997; ). Comparison of agar dilution, broth microdilution, E-test, disk diffusion, and automated Vitek methods for testing susceptibilities of Enterococcus spp. to vancomycin. J Clin Microbiol 35, 3258-3263.
    [Google Scholar]
  14. Koland, J. G. & Hammes, G. G. ( 1986; ). Steady state kinetic studies of purified yeast plasma membrane proton-translocating ATPase. J Biol Chem 261, 5936-5942.
    [Google Scholar]
  15. Lapathitis, G. & Kotyk, A. ( 1998; ). Different sources of acidity in glucose-elicited extracellular acidification in the yeast Saccharomyces cerevisiae. Biochem Mol Biol Int 46, 973-978.
    [Google Scholar]
  16. Machida, K., Tanaka, T., Shibata, K. & Taniguchi, M. ( 1997; ). Inhibitory effects of nucleotide 5′-alkylphosphate on sexual agglutination in Saccharomyces cerevisiae. FEMS Microbiol Lett 147, 17-22.[CrossRef]
    [Google Scholar]
  17. Machida, K., Tanaka, T., Fujita, K. & Tanaguchi, M. ( 1998; ). Farnesol-induced generation of reactive oxygen species via indirect inhibition of the mitochondrial electron transport chain in the yeast Saccharomyces cerevisiae. J Bacteriol 180, 4460-4465.
    [Google Scholar]
  18. Machida, K., Tanaka, T., Yano, Y., Otani, S. & Taniguchi, M. ( 1999; ). Farnesol-induced growth inhibition in Saccharomyces cerevisiae by a cell cycle mechanism. Microbiology 145, 293-299.[CrossRef]
    [Google Scholar]
  19. Manfredi, J. P., Klein, C., Herrero, J. J., Byrd, D. A., Trueheart, J., Wiesler, W. T., Fowlkes, D. M. & Broach, J. R. ( 1996; ). Yeast alpha mating factor structure–activity relationship derived from genetically selected peptide agonists and antagonists of Ste2p. Mol Cell Biol 16, 4700-4709.
    [Google Scholar]
  20. Melnykovych, G., Haug, J. S. & Goldner, C. M. ( 1992; ). Growth inhibition of leukemia cell line CEM-C1 by farnesol: effects of phosphatidylcholine and diacylglycerol. Biochem Biophys Res Commun 186, 543-548.[CrossRef]
    [Google Scholar]
  21. Monk, B. C., Mason, A. B., Abramochkin, G., Haber, J. E., Seto-Young, D. & Perlin, D. S. ( 1995; ). The yeast plasma membrane proton pumping ATPase is a viable antifungal target. I. Effects of the cysteine-modifying reagent omeprazole. Biochim Biophys Acta 1239, 81-90.[CrossRef]
    [Google Scholar]
  22. Morishita, T., Mitsuzawa, H., Nakafuku, M., Nakamura, S., Hattori, S. & Anraku, Y. ( 1995; ). Requirement of Saccharomyces cerevisiae Ras for completion of mitosis. Science 270, 1213-1215.[CrossRef]
    [Google Scholar]
  23. Ogita, K., Miyamoto, S., Koide, H. & 7 other authors ( 1990; ). Protein kinase C in Saccharomyces cerevisiae: comparison with the mammalian enzyme. Proc Natl Acad Sci USA 87, 5011–5015.[CrossRef]
    [Google Scholar]
  24. Omura, S. ( 1976; ). The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis. Bacteriol Rev 40, 681-697.
    [Google Scholar]
  25. Preiss, J., Loowis, C. R., Bishop, R. W., Stein, R., Niedel, J. E. & Bell, R. M. ( 1986; ). Quantitative measurement of sn-1, 2-diacylglycerols present in platelets, hepatocytes, and ras- and sis-transformed normal rat kidney cells. J Biol Chem 616, 8597-8600.
    [Google Scholar]
  26. Rodriguez, R. J. & Parks, L. W. ( 1981; ). Physiological response of Saccharomyces cerevisiae to 15-azasterol-mediated growth inhibition. Antimicrob Agents Chemother 20, 184-189.[CrossRef]
    [Google Scholar]
  27. Rosa, M. F. & Sá-Correia, I. ( 1991; ). In vivo activation by ethanol of plasma membrane ATPase of Saccharomyces cerevisiae. Appl Environ Microbiol 57, 830-835.
    [Google Scholar]
  28. Serrano, R. ( 1989; ). Structure and function of plasma membrane ATPase. Annu Rev Plant Physiol 40, 61-94.[CrossRef]
    [Google Scholar]
  29. Serrano, R., Kielland-Brandt, M. C. & Fink, G. R. ( 1986; ). Yeast plasma membrane ATPase is essential for growth and has homology with (Na+, K+), K+- and Ca2+-ATPases. Nature 319, 689-693.[CrossRef]
    [Google Scholar]
  30. Shiraishi, T., Tezuka, K. & Uda, Y. ( 1994; ). Selective inhibition of lignoceroyl-CoA synthase by adenosine 5′-alkylphosphates. FEBS Lett 352, 353-355.[CrossRef]
    [Google Scholar]
  31. Tomoda, H., Igarashi, K., Cyong, J. C. & Omura, S. ( 1991; ). Evidence for an essential role of long chain acyl-CoA synthetase in animal cell proliferation: inhibition of long chain acyl-CoA synthetase by triacsins caused inhibition of Raji cell proliferation. J Biol Chem 266, 4214-4219.
    [Google Scholar]
  32. Ueki, M., Abe, K., Hanafi, M., Shibata, K., Tanaka, T. & Taniguchi, M. ( 1996; ). UK-2A, B, C and D, novel antifungal antibiotics from Streptomyces sp. 517–02. I. Fermentation, isolation, and biological properties. J Antibiot 49, 639-643.[CrossRef]
    [Google Scholar]
  33. Voziyan, P. A., Haug, J. S. & Melnykovych, G. ( 1995; ). Mechanism of farnesol cytotoxicity: further evidence for the role of PKC-dependent signal transduction in farnesol-induced apoptotic cell death. Biochem Biophys Res Commun 212, 479-486.[CrossRef]
    [Google Scholar]
  34. Wach, A., Ahlers, J. & Graeber, P. ( 1990; ). The proton-ATPase of the plasma membrane from yeast: kinetics of ATP hydrolysis in native membranes, isolated and reconstituted enzymes. Eur J Biochem 189, 675-682.[CrossRef]
    [Google Scholar]
  35. Yasuda, T. & Inoue, Y. ( 1983; ). Steady-state kinetic studies of binding and catalysis by ribonuclease T2: a microenvironment survey of the active site by using a series of adenosine-3′- and -5′-alkylphosphates. J Biochem 94, 1475-1481.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-146-2-377
Loading
/content/journal/micro/10.1099/00221287-146-2-377
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error