Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Sep;86(17):6626–6629. doi: 10.1073/pnas.86.17.6626

K+/H+-antiporter nigericin arrests DNA synthesis in Ehrlich ascites carcinoma cells.

L B Margolis 1, Y u Novikova I 1, I A Rozovskaya 1, V P Skulachev 1
PMCID: PMC297897  PMID: 2771947

Abstract

Acidification of the cytoplasm of Ehrlich ascites carcinoma cells to pH 6.3 arrests DNA synthesis in these cells. Such an effect can be achieved by incubating the cells at pH 6.2 or by adding low concentrations of the K+/H+ antiporter, the antibiotic nigericin, at neutral pH. Glucose and anaerobiosis potentiate the nigericin effect. The inhibition of DNA synthesis by nigericin occurs without any significant decrease in the ATP concentration and in the mitochondrial membrane potential. The DNA synthesis inhibition is caused neither by a decrease in the intracellular [K+] nor by an increase in the intracellular [Na+] accompanying the nigericin effect (at least at low concentrations of the antibiotic). Nigericin should thus be regarded as a type of a cytostatic primarily affecting intracellular pH.

Full text

PDF
6626

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bierman A. J., Tertoolen L. G., de Laat S. W., Moolenaar W. H. The Na+/H+ exchanger is constitutively activated in P19 embryonal carcinoma cells, but not in a differentiated derivative. Responsiveness to growth factors and other stimuli. J Biol Chem. 1987 Jul 15;262(20):9621–9628. [PubMed] [Google Scholar]
  2. Hagag N., Lacal J. C., Graber M., Aaronson S., Viola M. V. Microinjection of ras p21 induces a rapid rise in intracellular pH. Mol Cell Biol. 1987 May;7(5):1984–1988. doi: 10.1128/mcb.7.5.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Johnson L. V., Walsh M. L., Chen L. B. Localization of mitochondria in living cells with rhodamine 123. Proc Natl Acad Sci U S A. 1980 Feb;77(2):990–994. doi: 10.1073/pnas.77.2.990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Lagarde A. E., Franchi A. J., Paris S., Pouysségur J. M. Effect of mutations affecting Na+: H+ antiport activity on tumorigenic potential of hamster lung fibroblasts. J Cell Biochem. 1988 Mar;36(3):249–260. doi: 10.1002/jcb.240360306. [DOI] [PubMed] [Google Scholar]
  5. Margolis L. B., Rozovskaja I. A., Skulachev V. P. Acidification of the interior of Ehrlich ascites tumor cells by nigericin inhibits DNA synthesis. FEBS Lett. 1987 Aug 17;220(2):288–290. doi: 10.1016/0014-5793(87)80831-1. [DOI] [PubMed] [Google Scholar]
  6. Moolenaar W. H. Effects of growth factors on intracellular pH regulation. Annu Rev Physiol. 1986;48:363–376. doi: 10.1146/annurev.ph.48.030186.002051. [DOI] [PubMed] [Google Scholar]
  7. Ober S. S., Pardee A. B. Intracellular pH is increased after transformation of Chinese hamster embryo fibroblasts. Proc Natl Acad Sci U S A. 1987 May;84(9):2766–2770. doi: 10.1073/pnas.84.9.2766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Paradiso A. M., Tsien R. Y., Machen T. E. Na+-H+ exchange in gastric glands as measured with a cytoplasmic-trapped, fluorescent pH indicator. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7436–7440. doi: 10.1073/pnas.81.23.7436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Pouysségur J., Franchi A., L'Allemain G., Paris S. Cytoplasmic pH, a key determinant of growth factor-induced DNA synthesis in quiescent fibroblasts. FEBS Lett. 1985 Oct 7;190(1):115–119. doi: 10.1016/0014-5793(85)80439-7. [DOI] [PubMed] [Google Scholar]
  10. Rotin D., Wan P., Grinstein S., Tannock I. Cytotoxicity of compounds that interfere with the regulation of intracellular pH: a potential new class of anticancer drugs. Cancer Res. 1987 Mar 15;47(6):1497–1504. [PubMed] [Google Scholar]
  11. Thomas J. A., Buchsbaum R. N., Zimniak A., Racker E. Intracellular pH measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situ. Biochemistry. 1979 May 29;18(11):2210–2218. doi: 10.1021/bi00578a012. [DOI] [PubMed] [Google Scholar]
  12. Vigne P., Frelin C., Lazdunski M. The Na+-dependent regulation of the internal pH in chick skeletal muscle cells. The role of the Na+/H+ exchange system and its dependence on internal pH. EMBO J. 1984 Aug;3(8):1865–1870. doi: 10.1002/j.1460-2075.1984.tb02060.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES