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Participation of phenolic acids of microbial origin in the dysfunction of mitochondria in sepsis

Abstract

The role of low-molecular-weight phenolic acids of microbial origin in the mitochondrial dysfunction observed in sepsis has been studied. It was shown that microbial phenolic acids formed during fermentation of aromatic amino acids and polyphenols have an effect on mitochondrial functions, whose magnitude depends on the structure of a particular phenolic acid. The anaerobic metabolites cinnamic and benzoic acids and, to a lesser extent, phenylpropionic and phenylacetic acids at concentrations of 0.02–0.1 mM inhibited the NAD-dependent respiration, decreased the Ca2+-retention capacity of mitochondria, and oxidized the thiol groups. Their effects were partially abolished by menadione and dithiothreitol. Hydroxylated phenolic acids, 2,4-dihydroxybenzoic, 2,3-dihydroxyphenylpropionic, and other phenolic acids formed in aerobic metabolism of bacteria, when used at the same concentrations, did not affect these processes. During the catabolism of phenolic acids by clinically important bacteria, these compounds undergo anaerobic interconversions. The data obtained suggest that they contribute to the mitochondrial dysfunction in sepsis, and this contribution increases under hypoxic conditions.

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References

  1. Pinsky, M.R., Sepsis and Multiple Organ Failure, Contrib. Nephrol., 2007, vol. 156, pp. 47–63.

    Article  CAS  PubMed  Google Scholar 

  2. Fink, M.P., Bench-to-Bedside Review: Cytopathic Hypoxia, Critical Care, 2002, vol. 6, pp. 491–499.

    Article  PubMed  Google Scholar 

  3. Sriskandan, S. and Altmann, D.M., The Immunology of Sepsis, J. Pathol., 2008, vol. 214, no 2, pp. 211–223.

    Article  CAS  PubMed  Google Scholar 

  4. Protti, A. and Singer, M., Bench-to-Bedside Review: Potential Strategies to Protect or Reverse Mitochondrial Dysfunction in Sepsis-Induced Organ Failure, Critical Care, 2006, vol. 10, no 5, pp. 228–235.

    Article  PubMed  Google Scholar 

  5. Crouse, E.D., Mitochondrial Dysfunction in Septic Shock and Multiple Organ Dysfunction Syndrome, Mitochondrion, 2004, vol. 4, pp. 729–741.

    Article  Google Scholar 

  6. Levy, R.J., Mitochondrial Dysfunction, Bioenergetic Impairment, and Metabolic Down-Regulation in Sepsis, Shock, 2007, vol. 28, pp. 24–28.

    Article  CAS  PubMed  Google Scholar 

  7. Levy, R.J. and Deutschman, C.S., Cytochrome c Oxidase Dysfunction in Sepsis, Crit. Care Med., 2007, vol. 35, no 9, pp. 468–475.

    Article  Google Scholar 

  8. Larche, J., Lancel, S., Hassoun, S.M., Favory, R., Decoster, B., Marchetti, P., Chopin, C. and Neviere, R., Inhibition of Mitochondrial Permeability Transition Prevents Sepsis-Induced Myocardial Dysfunction and Mortality, J. Am. Coll. Cardiol, 2006, vol. 48, pp. 377–385.

    Article  CAS  PubMed  Google Scholar 

  9. Beloborodova, N.V., Arkhipova, A.S., Beloborodov, D.M., Boiko, N.B., Melko, A.I., and Olenin, A.Yu., Chromatography-Mass Spectrometric Detection of Low-Molecular-Weight Phenolic Compounds Originating from Microbes in the Serum from Patients with Sepsis, Klin. Lab. Diagn. (Rus), 2006, vol. 2, pp. 3–6.

    Google Scholar 

  10. Beloborodova, N.V. and Osipov, G.A., Small Molecules Originating from Microbes (SMOM) and Their Role in Microbes-Host Relationship, Microbial Ecology in Health and Disease, 2000, vol. 12, pp. 12–21.

    Article  CAS  Google Scholar 

  11. Khodakova, A. and Beloborodova, N., Microbial Metabolites in the Blood of Patients with Sepsis, Crit. Care, 2007, vol. 11, pp. 5.

    Article  Google Scholar 

  12. Fedotcheva, N.I., Kazakov, R.E., Kondrashova, M.N. and Beloborodova, N.V., Toxic Effects of Microbial Phenolic Acids on the Functions of Mitochondria, Toxicol. Lett., 2008, vol. 180. pp. 182–188.

    Article  CAS  PubMed  Google Scholar 

  13. Teplova, V.V., Kruglov, A.G., Morkunaite, S., and Saris, N.-E., Generation of Superoxide Anion and the Induction of Nonspecific Permeability in Mitochondria by Dihydrolipoic Acid, Biol. Membrany (Rus.), 2002, vol. 19, no 4, pp. 297–302.

    CAS  Google Scholar 

  14. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J., Protein Measurement with the Folin Phenol Reagent, J. Biol. Chem., 1951, vol. 193, pp. 265–275.

    CAS  PubMed  Google Scholar 

  15. Kamo, N., Muratsugu, M., Hongoh, R., and Kobatake, Y., Membrane Potential of Mitochondria Measured with an Electrode Sensitive to Tetraphenyl Phosphonium and Relationship between Proton Electrochemical Potential and Phosphorylation Potential in Steady State, Membr. Biol., 1979, vol. 49, pp. 105–121.

    Article  CAS  Google Scholar 

  16. Saris, N.-E. and Allshire, A. Calcium Ion Transport in Mitochondria, Methods Enzymol., 1989, vol. 174, pp. 68–85.

    Article  CAS  PubMed  Google Scholar 

  17. Custodio, J.B., Palmeira, C.M., Moreno, A.J., and Wallace K.B., Acrylic Acid Induces the GlutathioneIndependent Mitochondrial Permeability Transition in Vitro, Toxicol Sci., 1998, vol. 43, pp. 19–27.

    CAS  PubMed  Google Scholar 

  18. Bugg, T.D., Overproduction, Purification and Properties of 2,3-Dihydroxyphenylpropionate 1,2-Dioxygenase from Escherichia coli, Biochim. Biophys. Acta., 1993, vol. 1202, no 1, pp. 258–264.

    CAS  PubMed  Google Scholar 

  19. Schlosrich, J., Eley, K.L., Crowley, P.J., and Bugg, T.D., Directed Evolution of a Non-Heme-Iron-Dependent Extradiol Catechol Dioxygenase: Identification of Mutants with Intradiol Oxidative Cleavage Activity, Chembiochem., 2006, vol. 7, no 12, pp. 1899–1908.

    Article  CAS  PubMed  Google Scholar 

  20. Steele, M., Gyles, C., Chan, V.L., and Odumeru, J., Monoclonal Antibodies Specific for Hippurate Hydrolase of Campylobacter jejuni, J. Clin. Microbiol., 2002, vol. 40, no 3, pp. 1080–1082.

    Article  CAS  PubMed  Google Scholar 

  21. Krause, G. and Simon, H., Design and Applications of Sensitive Enzyme Immunoassays Specific for Clostridial Enoate Reductases, Z. Naturforsch. C, 1989, vol. 44, nos. 5–6, pp. 345–352.

    CAS  PubMed  Google Scholar 

  22. Boll, M. and Fuchs, G., Identification and Characterization of the Natural Electron Donor Ferredoxin and of FAD as a Possible Prosthetic Group of Benzoyl-CoA Reductase (Dearomatizing), a Key Enzyme of Anaerobic Aromatic Metabolism, Eur. J. Biochem., 1998, vol. 251, no 3, pp. 946–954.

    Article  CAS  PubMed  Google Scholar 

  23. Barnes, M.R., Duetz, W.A., and Williams, P.A., A 3-(3-Hydroxyphenyl)propionic Acid Catabolic Pathway in Rhodococcus globerulus PWD1: Cloning and Characterization of the hpp Operon, J. Bacteriol., 1997, vol. 179, no 19, pp. 6145–6153.

    CAS  PubMed  Google Scholar 

  24. Waldecker, M., Kautenburger, T., Daumann, H., Busch, C., and Schrenk D., Inhibition of Histone-Deacetylase Activity by Short-Chain Fatty Acids and Some Polyphenol Metabolites Formed in the Colon, J. Nutr. Biochem., 2008, vol. 19, no 9, pp. 587–593.

    Article  CAS  PubMed  Google Scholar 

  25. Xiang, L. and Moore, B.S., Inactivation, Complementation, and Heterologous Expression of encP, a Novel Bacterial Phenylalanine Ammonia-Lyase Gene, J. Biol. Chem., 2002, vol. 277, no 36, pp. 32505–32509.

    Article  CAS  PubMed  Google Scholar 

  26. Jenner, A.M., Rafter, J., and Halliwell, B., Human Fecal Water Content of Phenolics: The Extent of Colonic Exposure to Phenolic Compounds, Free Radic. Biol. Med., 2005, vol. 38, pp. 763–772.

    Article  CAS  PubMed  Google Scholar 

  27. Mayrand, D. and Bourgeau, G., Production of Phenylacetic Acid by Anaerobes, J. Clin. Microb., 1982, vol. 16, pp. 747–750.

    CAS  Google Scholar 

  28. Schmidt, S., Westhoff, T.H., Krauser, P., Zidek, W., and van der Giet M., The Uraemic Toxin Phenylacetic Acid Increases the Formation of Reactive Oxygen Species in Vascular Smooth Muscle Cells, Neprol. Dial. Transplant., 2008, vol. 23, pp. 65–71.

    Article  CAS  Google Scholar 

  29. Karlsson, P.C., Huss, U., Jenner, A., Halliwell, B., Bohlin, L., and Rafte, J.J., Human Fecal Water Inhibits COX-2 in Colonic HT-29 Cells: Role of Phenolic Compounds, J. Nutr., 2005, vol. 135, pp. 2343–2349.

    CAS  PubMed  Google Scholar 

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Correspondence to N. I. Fedotcheva.

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Original Russian Text © N.I. Fedotcheva, V.V. Teplova, N.V. Beloborodova, 2010, published in Biologicheskie Membrany, 2010, Vol. 27, No. 1, pp. 60–66.

The article was translated by the authors.

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Fedotcheva, N.I., Teplova, V.V. & Beloborodova, N.V. Participation of phenolic acids of microbial origin in the dysfunction of mitochondria in sepsis. Biochem. Moscow Suppl. Ser. A 4, 50–55 (2010). https://doi.org/10.1134/S1990747810010083

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  • DOI: https://doi.org/10.1134/S1990747810010083

Key words

  • phenolic acids
  • sepsis
  • hypoxia
  • thiol groups
  • dysfunction of mitochondria