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Effects of α-ketoglutarate on neutrophil intracellular amino and α-keto acid profiles and ROS production

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Abstract

The aim of this study was to determine the effects of α-ketoglutarate on neutrophil (PMN), free α-keto and amino-acid profiles as well as important reactive oxygen species (ROS) produced [superoxide anion (O2 −), hydrogen peroxide (H2O2)] and released myeloperoxidase (MPO) acitivity. Exogenous α-ketoglutarate significantly increased PMN α-ketoglutarate, pyruvate, asparagine, glutamine, asparatate, glutamate, arginine, citrulline, alanine, glycine and serine in a dose as well as duration of exposure dependent manner. Additionally, in parallel with intracellular α-ketoglutarate changes, increases in O2 – formation, H2O2-generation and MPO acitivity have also been observed. We therefore believe that α-ketoglutarate is important for affecting PMN “susceptible free amino- and α-keto acid pools” although important mechanisms and backgrounds are not yet completely explored. Moreover, our results also show very clearly that changes in intragranulocytic α-ketoglutarate levels are relevant metabolic determinants in PMN nutrition considerably influencing and modulating the magnitude and quality of the granulocytic host defense capability as well as production of ROS.

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Authors and Affiliations

  1. Clinics of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Giessen and Marburg GmbH, Justus-Liebig-University Giessen, Rudolf-Buchheim-Strasse 7, 35385, Giessen, Germany

    Jörg Mühling, F. Tussing, K. A. Nickolaus, R. Matejec, M. Henrich, H. Harbach, M. Wolff, K. Weismüller, J. Engel, T. W. Langefeld & M. A. Weigand

  2. University Department of Anaesthesia, Royal Liverpool University Hospital, Liverpool, UK

    I. D. Welters

  3. Dr. Ing. Herbert Knauer GmbH, Berlin, Germany

    M. Fuchs

  4. Department of Cardiovascular Surgery, University Hospital Giessen and Marburg, Justus-Liebig-University Giessen, Giessen, Germany

    M. C. Heidt

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  1. Jörg Mühling
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  2. F. Tussing
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  3. K. A. Nickolaus
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  4. R. Matejec
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  5. M. Henrich
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  6. H. Harbach
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  7. M. Wolff
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  8. K. Weismüller
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  9. J. Engel
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  10. I. D. Welters
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  11. T. W. Langefeld
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  12. M. Fuchs
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  14. M. C. Heidt
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Correspondence to Jörg Mühling.

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Mühling, J., Tussing, F., Nickolaus, K.A. et al. Effects of α-ketoglutarate on neutrophil intracellular amino and α-keto acid profiles and ROS production. Amino Acids 38, 167–177 (2010). https://doi.org/10.1007/s00726-008-0224-5

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