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. 1992 Sep 1;286(Pt 2):597–602. doi: 10.1042/bj2860597

Dual effect of spermine on mitochondrial Ca2+ transport.

S Lenzen 1, W Münster 1, I Rustenbeck 1
PMCID: PMC1132939  PMID: 1530590

Abstract

1. A dual effect of the polyamine spermine on Ca2+ uptake by isolated rat liver, brain and heart mitochondria could be demonstrated by using a high-resolution system for studying mitochondrial Ca2+ transport. Depending on the experimental situation, spermine had an inhibiting or accelerating effects on mitochondrial Ca(2+)-uptake rate, but invariably increased the mitochondrial Ca2+ accumulation. 2. Both effects were concentration-dependent and clearly discernible on the basis of their different kinetic characteristics. For mitochondria from all three tissues the half-maximally effective concentration for inhibition of the initial rate of Ca2+ uptake was approx. 180 microM, whereas that for the subsequent stimulation of Ca2+ accumulation was approx. 50 microM. 3. Acceleration of the initial uptake rate could be seen when the mitochondria were preloaded with spermine during a 2 min preincubation period and thereafter incubated in a medium without spermine. 4. When such spermine-preloaded mitochondria were incubated in a spermine-containing medium, the increase in Ca(2+)-accumulation capacity was maintained in spite of an unchanged rate of Ca2+ uptake. 5. Mg2+ interacted with the effects of spermine in a differential manner, enhancing the initial inhibition of the rate of mitochondrial Ca2+ uptake and diminishing the subsequent stimulation of mitochondrial Ca2+ accumulation. 6. This dual effect of spermine on mitochondrial Ca2+ transport resolves the apparent paradox that a polycationic compound can act as a stimulator of Ca2+ uptake.

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Selected References

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  1. Akerman K. E. Effect of Mg2+ and spermine on the kinetics of Ca2+ transport in rat-liver mitochondria. J Bioenerg Biomembr. 1977 Feb;9(1):65–72. doi: 10.1007/BF00745043. [DOI] [PubMed] [Google Scholar]
  2. Becker G. L., Fiskum G., Lehninger A. L. Regulation of free Ca2+ by liver mitochondria and endoplasmic reticulum. J Biol Chem. 1980 Oct 10;255(19):9009–9012. [PubMed] [Google Scholar]
  3. Byczkowski J. Z., Zychlinski L., Porter C. W. Inhibition of the bioenergetic functions of isolated rat liver mitochondria by polyamines. Biochem Pharmacol. 1982 Dec 15;31(24):4045–4053. doi: 10.1016/0006-2952(82)90654-2. [DOI] [PubMed] [Google Scholar]
  4. Canellakis E. S., Viceps-Madore D., Kyriakidis D. A., Heller J. S. The regulation and function of ornithine decarboxylase and of the polyamines. Curr Top Cell Regul. 1979;15:155–202. [PubMed] [Google Scholar]
  5. Chaffee R. R., Salganicoff L., Arine R. M., Rochelle R. H., Schultz E. L. Polyamine effects on succinate-linked and alphaketoglutarate- linked rat liver mitochondrial respiration. Biochem Biophys Res Commun. 1977 Aug 8;77(3):1009–1016. doi: 10.1016/s0006-291x(77)80078-8. [DOI] [PubMed] [Google Scholar]
  6. Corkey B. E., Duszynski J., Rich T. L., Matschinsky B., Williamson J. R. Regulation of free and bound magnesium in rat hepatocytes and isolated mitochondria. J Biol Chem. 1986 Feb 25;261(6):2567–2574. [PubMed] [Google Scholar]
  7. Fan C. C., Koenig H. The role of polyamines in beta-adrenergic stimulation of calcium influx and membrane transport in rat heart. J Mol Cell Cardiol. 1988 Sep;20(9):789–799. doi: 10.1016/s0022-2828(88)80004-x. [DOI] [PubMed] [Google Scholar]
  8. Fiskum G. Intracellular levels and distribution of Ca2+ in digitonin-permeabilized cells. Cell Calcium. 1985 Apr;6(1-2):25–37. doi: 10.1016/0143-4160(85)90032-6. [DOI] [PubMed] [Google Scholar]
  9. Gylfe E. Insulin secretagogues induce Ca(2+)-like changes in cytoplasmic Mg2+ in pancreatic beta-cells. Biochim Biophys Acta. 1990 Oct 15;1055(1):82–86. doi: 10.1016/0167-4889(90)90094-t. [DOI] [PubMed] [Google Scholar]
  10. Heby O., Persson L. Molecular genetics of polyamine synthesis in eukaryotic cells. Trends Biochem Sci. 1990 Apr;15(4):153–158. doi: 10.1016/0968-0004(90)90216-x. [DOI] [PubMed] [Google Scholar]
  11. Jensen J. R., Lynch G., Baudry M. Allosteric activation of brain mitochondrial Ca2+ uptake by spermine and by Ca2+: developmental changes. J Neurochem. 1989 Oct;53(4):1173–1181. doi: 10.1111/j.1471-4159.1989.tb07411.x. [DOI] [PubMed] [Google Scholar]
  12. Jensen J. R., Lynch G., Baudry M. Polyamines stimulate mitochondrial calcium transport in rat brain. J Neurochem. 1987 Mar;48(3):765–772. doi: 10.1111/j.1471-4159.1987.tb05583.x. [DOI] [PubMed] [Google Scholar]
  13. Jung D. W., Apel L., Brierley G. P. Matrix free Mg2+ changes with metabolic state in isolated heart mitochondria. Biochemistry. 1990 May 1;29(17):4121–4128. doi: 10.1021/bi00469a015. [DOI] [PubMed] [Google Scholar]
  14. Jänne J., Pösö H., Raina A. Polyamines in rapid growth and cancer. Biochim Biophys Acta. 1978 Apr 6;473(3-4):241–293. doi: 10.1016/0304-419x(78)90015-x. [DOI] [PubMed] [Google Scholar]
  15. Kröner H. Spermine, another specific allosteric activator of calcium uptake in rat liver mitochondria. Arch Biochem Biophys. 1988 Nov 15;267(1):205–210. doi: 10.1016/0003-9861(88)90024-0. [DOI] [PubMed] [Google Scholar]
  16. Lenzen S., Hickethier R., Panten U. Interactions between spermine and Mg2+ on mitochondrial Ca2+ transport. J Biol Chem. 1986 Dec 15;261(35):16478–16483. [PubMed] [Google Scholar]
  17. Lenzen S., Panten U. A versatile Ca2+ ion-sensitive minielectrode with a microincubation chamber. Anal Biochem. 1985 Sep;149(2):301–308. doi: 10.1016/0003-2697(85)90574-3. [DOI] [PubMed] [Google Scholar]
  18. Lenzen S., Rustenbeck I. Effects of IP3, spermine, and Mg2+ on regulation of Ca2+ transport by endoplasmic reticulum and mitochondria in permeabilized pancreatic islets. Diabetes. 1991 Mar;40(3):323–326. doi: 10.2337/diab.40.3.323. [DOI] [PubMed] [Google Scholar]
  19. Lenzen S., Schmidt W., Panten U. Transamination of neutral amino acids and 2-keto acids in pancreatic B-cell mitochondria. J Biol Chem. 1985 Oct 15;260(23):12629–12634. [PubMed] [Google Scholar]
  20. McCormack J. G. Effects of spermine on mitochondrial Ca2+ transport and the ranges of extramitochondrial Ca2+ to which the matrix Ca2+-sensitive dehydrogenases respond. Biochem J. 1989 Nov 15;264(1):167–174. doi: 10.1042/bj2640167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McKnight G. S. A colorimetric method for the determination of submicrogram quantities of protein. Anal Biochem. 1977 Mar;78(1):86–92. doi: 10.1016/0003-2697(77)90011-2. [DOI] [PubMed] [Google Scholar]
  22. Mustelin T., Pösö H., Lapinjoki S. P., Gynther J., Andersson L. C. Growth signal transduction: rapid activation of covalently bound ornithine decarboxylase during phosphatidylinositol breakdown. Cell. 1987 Apr 24;49(2):171–176. doi: 10.1016/0092-8674(87)90557-5. [DOI] [PubMed] [Google Scholar]
  23. Nicchitta C. V., Williamson J. R. Spermine. A regulator of mitochondrial calcium cycling. J Biol Chem. 1984 Nov 10;259(21):12978–12983. [PubMed] [Google Scholar]
  24. Pegg A. E. Recent advances in the biochemistry of polyamines in eukaryotes. Biochem J. 1986 Mar 1;234(2):249–262. doi: 10.1042/bj2340249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Phillips J. E., Chaffee R. R. Restorative effects of spermine on oxidative phosphorylation and respiration in heat-aged mitochondria. Biochem Biophys Res Commun. 1982 Sep 16;108(1):174–181. doi: 10.1016/0006-291x(82)91847-2. [DOI] [PubMed] [Google Scholar]
  26. Rottenberg H., Marbach M. Regulation of Ca2+ transport in brain mitochondria. I. The mechanism of spermine enhancement of Ca2+ uptake and retention. Biochim Biophys Acta. 1990 Mar 15;1016(1):77–86. doi: 10.1016/0005-2728(90)90009-s. [DOI] [PubMed] [Google Scholar]
  27. Schuber F. Influence of polyamines on membrane functions. Biochem J. 1989 May 15;260(1):1–10. doi: 10.1042/bj2600001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. TABOR H., TABOR C. W. SPERMIDINE, SPERMINE, AND RELATED AMINES. Pharmacol Rev. 1964 Sep;16:245–300. [PubMed] [Google Scholar]
  29. Toninello A., Di Lisa F., Siliprandi D., Siliprandi N. Uptake of spermine by rat liver mitochondria and its influence on the transport of phosphate. Biochim Biophys Acta. 1985 May 28;815(3):399–404. doi: 10.1016/0005-2736(85)90366-9. [DOI] [PubMed] [Google Scholar]

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