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Apoptotic markers in the mitochondria, cytosol, and nuclei of brain cells during ammonia toxicity

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Abstract

The effects of toxic doses of ammonia on the induction of pro-apoptotic markers in rat brain cells were studied. It was found that neither induction of caspase-9 and caspase-3, nor changes in the membrane potential in nonsynaptic brain mitochondria, release of cytochrome c from mitochondria to cytosol, or apoptosis-inducing signals in the cell nuclei, were responsible for the ammonia toxicity in vivo. Thus, no evidence was found for any functional significance of mitochondria in cell death associated with acute hyperammonemia. The resistance of cell nuclei to ammonia-induced apoptosis could be caused either by a disordered translocation of the p53 protein from the cytosol into the nucleus or by translocation of its inactive form. The nonsynaptic brain mitochondria were also shown to be more resistant to the formation of nonspecific permeability pores and to Ca2+-induced swelling than cardiac and hepatic mitochondria and, as well, supported their membrane potential even under conditions of ammonia-stimulated production of active oxygen metabolites, excessive accumulation of Ca2+, oxidative stress, and impaired energy metabolism.

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Abbreviations

Ac-DEVD-pNa:

N-acetyl-Asp-Glu-Val-Asp-p-nitroanilide

Ac-LEHD-pNa:

N-acetyl-Leu-Glu-His-Asp-p-nitroanilide

Apaf-1:

apoptotic protease activating factor

CCCP:

carbonyl cyanide 3-chlorophenylhydrazone

CHAPS:

3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate

cyt-c :

cytochrome

c :

DOCh-Na, sodium deoxycholate

ELISA:

enzyme-linked immunosorbent assay

Mab:

monoclonal antibody

NPP:

the nonspecific permeability pore

PARP:

poly(ADP-ribose)polymerase

pNa:

p-nitroaniline

PMSF:

phenylmethanesulfonyl fluoride

PBS:

0.1 M phosphate buffer (pH 7.4)

RIPA:

buffer, a buffer solution containing 20 mM Tris-HCl (pH 7.5), 0.5 mM EDTA, 1% Nonidet, 0.5% sodium deoxycholate, 0.05% sodium dodecyl sulfate (SDS), 1 mM PMSF, 0.001 mg/ml aprotinin, and 0.002 mg/ml leupeptin

ssDNA:

DNA with single-strand break

TKM:

a buffer solution containing 10 mM Tris-HCl (pH 7.5), 2.5 mM KCl, and 5 mM MgCl2

Δω:

the potential of the internal mitochondrial membrane

TPP+ :

tetraphenylphosphonium ion

TS buffer:

Tris-sucrose buffer

References

  1. Kosenko, E., Kaminsky, Y., Stavroskaya, I.G., and Felipo, V., Brain. Res., 2000, vol. 880, no. 1–2, pp. 139–146.

    Article  PubMed  CAS  Google Scholar 

  2. Kosenko, E., Kaminsky, Y., Kaminsky, A., et al., Free Radic.Res., 1997, vol. 27, no. 6, pp. 637–644.

    Article  PubMed  CAS  Google Scholar 

  3. Kosenko, E., Kaminsky, Y., Lopata, O., et al., Metab. Brain Dis., 1998, vol. 13, no. 1, pp. 29–41.

    Article  PubMed  CAS  Google Scholar 

  4. Cande, C., Cecconi, F., Dessen, P., and Kroemer, G., J. Cell Sci., 2002, vol. 115, no. 24, pp. 4727–4734.

    Article  PubMed  CAS  Google Scholar 

  5. Kim, J.S., He, L., Qian, T., Lemasters, J.J., Curr. Mol. Med., 2003, vol. 3, no. 6, pp. 527–535.

    Article  PubMed  CAS  Google Scholar 

  6. Lemasters, J.J., Qian, T., Trost, L.C., et al., Biochem. Soc. Symp., 1999, vol. 66, pp. 205–222.

    PubMed  CAS  Google Scholar 

  7. Liu, X., Kim, C.N., Yang, J., et al., Cell, 1996, vol. 86, no. 1, pp. 147–157.

    Article  PubMed  CAS  Google Scholar 

  8. Kluck, R.M., Bossy-Wetzel, E., Green, D.R., and Newmeyer, D.D., Science, 1997, vol. 275, no. 5303, pp. 1132–1136.

    Article  PubMed  CAS  Google Scholar 

  9. Huang, H.M., Ou, H.C., Xu, H., et al., J. Neurosci. Res., 2003, vol. 74, no. 2, pp. 309–317.

    Article  PubMed  CAS  Google Scholar 

  10. Li, P., Nijhawan, D., Budihardjo, I., et al., Cell, 1997, vol. 91, no. 4, pp. 479–489.

    Article  PubMed  CAS  Google Scholar 

  11. Pan, G., O’Rourke, K., and Dixit, V.M., J. Biol. Chem., 1998, vol. 273, no. 10, pp. 5841–5845.

    Article  PubMed  CAS  Google Scholar 

  12. Susin, S.A., Lorenzo, H.K., Zamzami, N., et al., Nature, 1999, vol. 397, no. 6718, pp. 441–446.

    Article  PubMed  CAS  Google Scholar 

  13. Kastan, M.B., Onyekwere, O., Sidransky, D., et al., Cancer Res., 1991, vol. 51, no. 23, pp. 6304–6311.

    PubMed  CAS  Google Scholar 

  14. Kosenko, E., Montoliu, C., Giordano, G., et al., J. Neurochem., 2004, vol. 89, no. 5, pp. 1101–1110.

    Article  PubMed  CAS  Google Scholar 

  15. Jacobson, M.D., Burne, J.F., King, M.P., et al., Nature, 1993, vol. 361, no. 6410, pp. 365–369.

    Article  PubMed  CAS  Google Scholar 

  16. Kosenko, E., Venediktova, N., Kaminsky, Y., et al., Brain Res., 2003, vol. 981, no. 1–2, pp. 193–200.

    Article  PubMed  CAS  Google Scholar 

  17. Blobel, G. and Potter, V.R., Science, 1966, vol. 154, no. 757, pp. 1662–1665.

    Article  PubMed  CAS  Google Scholar 

  18. Kosenko, E., Felipo, V., Montoliu, C., et al., Metab. Brain Dis., 1997, vol. 12, no. 1, pp. 69–82.

    CAS  Google Scholar 

  19. Kosenko, E., Venediktova, N., Kaminsky, Y., et al., Brain Res. Brain Res. Protoc., 2001, vol. 7, no. 3, pp. 248–254.

    Article  PubMed  CAS  Google Scholar 

  20. Kamo, N., Muratsugu, M., Hongoh, R., and Kobatake, Y., J. Membr. Biol., 1979, vol. 49, no. 2, pp. 105–121.

    Article  PubMed  CAS  Google Scholar 

  21. Frankfurt, O.S. and Krishan, A., J. Immunol. Methods, 2001, vol. 253, no. 1–2, pp. 133–144.

    Article  PubMed  CAS  Google Scholar 

  22. Rotter, V., Abutbul, H., and Ben-Ze’ev, A., EMBO J., 1983, vol. 2, no. 7, pp. 1041–1047.

    PubMed  CAS  Google Scholar 

  23. Lane, D., Nature, 1998, vol. 394, no. 6694, pp. 616–617.

    Article  PubMed  CAS  Google Scholar 

  24. Prives, C. and Hall, P.A., J. Pathol., 1999, vol. 187, no. 1, pp. 112–126.

    Article  PubMed  CAS  Google Scholar 

  25. Bai, G., Rama Rao, K.V., Murthy, C.R., et al., J. Neurosci. Res., 2001, vol. 66, no. 5, pp. 981–991.

    Article  PubMed  CAS  Google Scholar 

  26. Hermenegildo, C., Monfort, P., and Felipo, V., Hepatology, 2000, vol. 31, no. 3, pp. 709–715.

    Article  PubMed  CAS  Google Scholar 

  27. Thornberry, N.A. and Lazebnik, Y., Science, 1998, vol. 281, no. 5381, pp. 1312–1316.

    Article  PubMed  CAS  Google Scholar 

  28. Krippner, A., Matsuno-Yagi, A., Gottlieb, R.A., and Babior, B.M., J. Biol. Chem., 1996, vol. 271, no. 35, pp. 21629–21636.

    Article  PubMed  CAS  Google Scholar 

  29. Rao, K.V., Mawal, Y.R., and Qureshi, I.A., Neurosci. Lett., 1997, vol. 224, no. 2, pp. 83–86.

    Article  PubMed  CAS  Google Scholar 

  30. Lazebnik, Y.A., Kaufmann, S.H., Desnoyers, S., et al., Nature, 1994, vol. 371, no. 6495, pp. 346–347.

    Article  PubMed  CAS  Google Scholar 

  31. Shah, G.M., Shah, R.G., and Poirier, G.G., Biochem. Biophys. Res. Commun., 1996, vol. 229, no. 3, pp. 838–844.

    Article  PubMed  CAS  Google Scholar 

  32. Chipuk, J.E., Kuwana, T., Bouchier-Hayes, L., et al., Science, 2004, vol. 303, no. 5660, pp. 1010–1014.

    Article  PubMed  CAS  Google Scholar 

  33. Li, Y., Chopp, M., Powers, C., and Jiang, N., Brain Res., 1997, vol. 765, no. 2, pp. 301–312.

    Article  PubMed  CAS  Google Scholar 

  34. Qu, L., Huang, S., Baltzis, D., et al., Genes Dev., 2004, vol. 18, no. 3, pp. 261–277.

    Article  PubMed  CAS  Google Scholar 

  35. Cui, H., Schroering, A., and Ding, H.F., Mol. Cancer Ther., 2002, vol. 1, no. 9, pp. 679–686.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow oblast, 142290, Russia

    Yu. G. Kaminsky

  2. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow oblast, 142290, Russia

    E. A. Kosenko & N. I. Venediktova

  3. Instituto de Investigaciones Citologicas, Valencia, Spain

    V. Felipo & C. Montoliu

Authors
  1. Yu. G. Kaminsky
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  2. E. A. Kosenko
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  3. N. I. Venediktova
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  4. V. Felipo
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  5. C. Montoliu
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Correspondence to Yu. G. Kaminsky.

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Original Russian Text © Yu.G. Kaminsky, E.A. Kosenko, N.I. Venediktova, V. Felipo, C. Montoliu, 2007, published in Neirokhimiya, 2006, Vol. 23, No. 3, pp. 208–216.

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Kaminsky, Y.G., Kosenko, E.A., Venediktova, N.I. et al. Apoptotic markers in the mitochondria, cytosol, and nuclei of brain cells during ammonia toxicity. Neurochem. J. 1, 78–85 (2007). https://doi.org/10.1134/S1819712407010114

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  • DOI: https://doi.org/10.1134/S1819712407010114

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