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Thiamine Mono- and Diphosphate Phosphatases in Bovine Brain Synaptosomes

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Abstract

Neurodegenerative diseases are accompanied by changes in the activity of thiamine mono- and diphosphate phosphatases, but molecular identification of these mammalian enzymes is incomplete. In this work, the protein fraction of bovine brain synaptosomes displaying phosphatase activity toward thiamine derivatives was subjected to affinity chromatography on thiamine-Sepharose. Protein fractions eluted with thiamine (pH 7.4 or 5.6), NaCl, and urea were assayed for the phosphatase activity against thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), and structurally similar purine nucleotides. Proteins in each fraction were identified by mass spectrometry using the SwissProt database for all organisms because of insufficient annotation of the bovine genome. Peptides of two annotated bacterial phosphatases, alkaline phosphatase L from the DING protein family and exopolyphosphatase, were identified in the acidic thiamine eluate. The abundance of peptides of alkaline phosphatase L and exopolyphosphatase in the eluted fractions correlated with ThMPase and ThDPase activities, respectively. The elution profiles of the ThMPase and ThDPase activities differed from the elution profiles of nucleotide phosphatases, thus indicating the specificity of these enzymes toward thiamine derivatives. The search for mammalian DING phosphatases in the eluates from thiamine-Sepharose revealed X-DING-CD4, mostly eluted by the acidic thiamine solution (pH 5.6). The identified exopolyphosphatase demonstrated structural similarity with apyrases possessing the ThDPase activity. The obtained results demonstrate that mammalian DING proteins and apyrases exhibit ThMPase and ThDPase activity, respectively.

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Abbreviations

DING:

protein family, named after the protein N-terminal tetrapeptide

HPBP:

human phosphate-binding DING protein

ThDP:

thiamine diphosphate

ThMP:

thiamine monophosphate

X-DING-CD4:

DING protein secreted by CD4+ T cells

References

  1. Bunik, V. I., and Aleshin, V. A. (2017) Analysis of the protein binding sites for thiamin and its derivatives to elucidate the molecular mechanisms of the noncoenzyme action of thiamin (vitamin B1), in Studies in Natural Products Chemistry, Elsevier, Amsterdam, Vol. 53, pp. 375–429, doi: https://doi.org/10.1016/b978-0-444-63930-1.00011-9

    Google Scholar 

  2. Aleshin, V. A., Mkrtchyan, G. V., and Bunik, V. I. (2019) Mechanisms of the non-coenzyme action of thiamin: protein targets and medical significance, Biochemistry (Moscow), 84, 829–850, doi: https://doi.org/10.1134/S0006297919080017.

    Article  CAS  Google Scholar 

  3. Hurt, J. K., Coleman, J. L., Fitzpatrick, B. J., TaylorBlake, B., Bridges, A. S., Vihko, P., and Zylka, M. J. (2012) Prostatic acid phosphatase is required for the antinociceptive effects of thiamine and benfotiamine, PLoS One, 7, e48562, doi: https://doi.org/10.1371/journal.pone.0048562

    Article  CAS  Google Scholar 

  4. Parkhomenko, Y. M., Protasova, Z. S., Yanchiy, O. R., Khosla, K., and Donchenko, G. V. (2001) Localization of thiamine-binding protein in synaptosomes from the rat brain, Neurophysiology, 33, 135–139, doi: https://doi.org/10.1023/a:1012840417285.

    Article  CAS  Google Scholar 

  5. Postoenko, V. A., Parkhomenko, Iu. M., Vovk, A. I., Khalmuradov, A. G., and Donchenko, G. V. (1987) Isolation and various properties of thiamine-binding protein from synaptosomes in the rat brain, Biokhimiya, 52, 1792–1797.

    CAS  Google Scholar 

  6. Pan, X., Sang, S., Fei, G., Jin, L., Liu, H., Wang, Z., Wang, H., and Zhong, C. (2017) Enhanced activities of blood thiamine diphosphatase and monophosphatase in Alzheimer’s disease, PLoS One, 12, e0167273, doi: https://doi.org/10.1371/journal.pone.0167273

    Article  Google Scholar 

  7. Sang, S., Pan, X., Chen, Z., Zeng, F., Pan, S., Liu, H., Jin, L., Fei, G., Wang, C., Ren, S., Jiao, F., Bao, W., Zhou, W., Guan, Y., Zhang, Y., Shi, H., Wang, Y., Yu, X., Wang, Y., and Zhong, C. (2018) Thiamine diphosphate reduction strongly correlates with brain glucose hypometabolism in Alzheimer’s disease, whereas amyloid deposition does not, Alzheimers Res. Ther., 10, 26, doi: https://doi.org/10.1186/s13195-018-0354-2.

    Article  Google Scholar 

  8. Diemer, H., Elias, M., Renault, F., Rochu, D., Contreras-Martel, C., Schaeffer, C., Van Dorsselaer, A., and Chabriere, E. (2008) Tandem use of X-ray crystallography and mass spectrometry to obtain ab initio the complete and exact amino acids sequence of HPBP, a human 38-kDa apolipoprotein, Proteins, 71, 1708–1720, doi: https://doi.org/10.1002/prot.21866.

    Article  CAS  Google Scholar 

  9. Renault, F., Chabriere, E., Andrieu, J. P., Dublet, B., Masson, P., and Rochu, D. (2006) Tandem purification of two HDL-associated partner proteins in human plasma, paraoxonase (PON1) and phosphate binding protein (HPBP) using hydroxyapatite chromatography, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 836, 15–21, doi: https://doi.org/10.1016/j.jchromb.2006.03.029.

    Article  CAS  Google Scholar 

  10. Gonzalez, D., Elias, M., and Chabriere, E. (2014) The DING family of phosphate binding proteins in inflammatory diseases, Adv. Exp. Med. Biol., 824, 27–32, doi: https://doi.org/10.1007/978-3-319-07320-04.

    Article  CAS  Google Scholar 

  11. Klyashchitsky, B. A., Pozdnev, V. F., Mitina, V. K., Voskoboev, A. I., and Chernikevich, I. P. (1980) Isolation and purification of biopolymers by biospecific affinity chromatography. Affinity chromatography of pyruvate decarboxylase from brewer’s yeast, Bioorg. Khim., 6, 1572–1579.

    Google Scholar 

  12. Mkrtchyan, G., Aleshin, V., Parkhomenko, Y., Kaehne, T., Di Salvo, M. L., Parroni, A., Contestabile, R., Vovk, A., Bettendorff, L., and Bunik, V. (2015) Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis, Sci. Rep., 5, 12583, doi: https://doi.org/10.1038/srep12583.

    Article  CAS  Google Scholar 

  13. Mezhenska, O. A., Aleshin, V. A., Kaehne, T., Artiukhov, A. V., and Bunik, V. I. (2020) Regulation of malate dehydrogenases and glutamate dehydrogenase in animal brain with thiamine in vitro and in vivo, Biochemistry (Moscow), 85, 27–39, doi: https://doi.org/10.1134/S0006297920010034

    Article  CAS  Google Scholar 

  14. Chan, K. M., Delfert, D., and Junger, K. D. (1986) A direct colorimetric assay for Ca2+-stimulated ATPase activity, Anal. Biochem., 157, 375–380, doi: https://doi.org/10.1016/0003-2697(86)90640-8.

    Article  CAS  Google Scholar 

  15. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951) Protein measurement with the Folin phenol reagent, J. Biol. Chem., 193, 265–275.

    CAS  PubMed  Google Scholar 

  16. Bunik, V., Kaehne, T., Degtyarev, D., Shcherbakova, T., and Reiser, G. (2008) Novel isoenzyme of 2-oxoglutarate dehydrogenase is identified in brain, but not in heart, FEBS J., 275, 4990–5006, doi: https://doi.org/10.1111/j.1742-4658.2008.06632.x

    Article  CAS  Google Scholar 

  17. Berna, A., Bernier, F., Chabriere, E., Perera, T., and Scott, K. (2008) DING proteins; novel members of a prokaryotic phosphate-binding protein superfamily which extends into the eukaryotic kingdom, Int. J. Biochem. Cell Biol., 40, 170–175, doi: https://doi.org/10.1016/j.biocel.2007.02.004.

    Article  CAS  Google Scholar 

  18. Collombet, J. M., Elias, M., Gotthard, G., Four, E., Renault, F., Joffre, A., Baubichon, D., Rochu, D., and Chabriere, E. (2010) Eukaryotic DING proteins are endogenous: an immunohistological study in mouse tissues, PLoS One, 5, e9099, doi: https://doi.org/10.1371/journal.pone.0009099

    Article  Google Scholar 

  19. Cherrier, T., Elias, M., Jeudy, A., Gotthard, G., Le Douce, V., Hallay, H., Masson, P., Janossy, A., Candolfi, E., Rohr, O., Chabriere, E., and Schwartz, C. (2011) Human-phosphate-binding-protein inhibits HIV-1 gene transcription and replication, Virol. J., 8, 352, doi: https://doi.org/10.1186/1743-422X-8-352

    Article  CAS  Google Scholar 

  20. Sachdeva, R., Li, Y., Shilpi, R. Y., and Simm, M. (2015) Human X-DING-CD4 mediates resistance to HIV-1 infection through novel paracrine-like signaling, FEBS J., 282, 937–950, doi: https://doi.org/10.1111/febs.13192

    Article  CAS  Google Scholar 

  21. Morales, R., Berna, A., Carpentier, P., Contreras-Martel, C., Renault, F., Nicodeme, M., Chesne-Seck, M. L., Bernier, F., Dupuy, J., Schaeffer, C., Diemer, H., Van-Dorsselaer, A., Fontecilla-Camps, J. C., Masson, P., Rochu, D., and Chabriere, E. (2006) Serendipitous discovery and X-ray structure of a human phosphate binding apolipoprotein, Structure, 14, 601–609, doi: https://doi.org/10.1016/j.str.2005.12.012.

    Article  CAS  Google Scholar 

  22. Lesner, A., Shilpi, R., Ivanova, A., Gawinowicz, M. A., Lesniak, J., Nikolov, D., and Simm, M. (2009) Identification of X-DING-CD4, a new member of human DING protein family that is secreted by HIV-1 resistant CD4+ T cells and has anti-viral activity, Biochem. Biophys. Res. Commun., 389, 284–289, doi: https://doi.org/10.1016/j.bbrc.2009.08.140.

    Article  CAS  Google Scholar 

  23. Ivanova, A., Shilpi, R. Y., Sachdeva, R., Li, G., and Simm, M. (2012) Native X-DING-CD4 protein secreted by HIV-1 resistant CD4+ T cells blocks activity of IL-8 promoter in human endothelial cells infected with enteric bacteria, Innate Immun., 18, 571–579, doi: https://doi.org/10.1177/1753425911427065

    Article  CAS  Google Scholar 

  24. Porzio, E., De Maio, A., Ricciardi, T., Mistretta, C., Manco, G., and Faraone-Mennella, M. R. (2018) Comparison of the DING protein from the archaeon Sulfolobus solfataricus with human phosphate-binding protein and Pseudomonas fluorescence DING counterparts, Extremophiles, 22, 177–188, doi: https://doi.org/10.1007/s00792-017-0985-4.

    Article  CAS  Google Scholar 

  25. Rochu, D., Renault, F., Clery-Barraud, C., Chabriere, E., and Masson, P. (2007) Stability of highly purified human paraoxonase (PON1): association with human phosphate binding protein (HPBP) is essential for preserving its active conformation(s), Biochim. Biophys. Acta, 1774, 874–883, doi: https://doi.org/10.1016/j.bbapap.2007.05.001.

    Article  CAS  Google Scholar 

  26. Vovk, A. I., Babii, L. V., and Murav’eva, I. V. (2002) Relative reactivity of thiamine monophosphate and thiamine diphosphate upon interaction with alkaline phosphatase, Ukr. Biokhim. Zh., 74, 93–96.

    CAS  Google Scholar 

  27. Beassoni, P. R., Gallarato, L. A., Boetsch, C., Garrido, M. N., and Lisa, A. T. (2015) Pseudomonas aeruginosa exopolyphosphatase is also a polyphosphate:ADP phosphotransferase, Enzyme Res., 2015, 404607, doi: https://doi.org/10.1155/2015/404607.

    Article  Google Scholar 

  28. Song, H., Dharmasena, M. N., Wang, C., Shaw, G. X., Cherry, S., Tropea, J. E., Jin, D. J., and Ji, X. (2019) Structure and activity of PPX/GppA homologs from Escherichia coli and Helicobacter pylori, FEBS J., doi: https://doi.org/10.1111/febs.15120

  29. Zebisch, M., Krauss, M., Schafer, P., Lauble, P., and Strater, N. (2013) Crystallographic snapshots along the reaction pathway of nucleoside triphosphate diphosphohy-drolases, Structure, 21, 1460–1475, doi: https://doi.org/10.1016/j.str.2013.05.016.

    Article  CAS  Google Scholar 

  30. Sano, S.-I., Matsuda, Y., Miyamoto, S., and Nakagawa, H. (1984) Thiamine pyrophosphatase and nucleoside diphosphatase in rat brain, Biochem. Biophys. Res. Commun., 118, 292–298, doi: https://doi.org/10.1016/0006-291x(84)91099-4.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991, Moscow, Russia

    V. A. Aleshin & V. I. Bunik

  2. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    V. A. Aleshin & V. I. Bunik

  3. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 01601, Kyiv, Ukraine

    O. A. Mezhenska & Y. M. Parkhomenko

  4. Institute of Experimental Internal Medicine, Otto von Guericke University, 39120, Magdeburg, Germany

    T. Kaehne

  5. Ministry of Health of the Russian Federation, Sechenov First Moscow State Medical University, 119991, Moscow, Russia

    V. I. Bunik

Authors
  1. V. A. Aleshin
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  2. O. A. Mezhenska
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  3. Y. M. Parkhomenko
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  4. T. Kaehne
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  5. V. I. Bunik
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Corresponding authors

Correspondence to V. A. Aleshin or V. I. Bunik.

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Funding

The work was supported by the Russian Foundation for Basic Research (project 18-34-00235).

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The authors declare no conflict of interest.

Ethical statement

All applicable international, national and institutional principles of animal care were satisfied. All animal experiments were performed according to the animal care regulations of the EU directive 2010/63/EU and approved by the Bioethics Committee of the Lomonosov Moscow State University.

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Aleshin, V.A., Mezhenska, O.A., Parkhomenko, Y.M. et al. Thiamine Mono- and Diphosphate Phosphatases in Bovine Brain Synaptosomes. Biochemistry Moscow 85, 378–386 (2020). https://doi.org/10.1134/S000629792003013X

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