Effects of alpha-ketoglutarate on neutrophil intracellular amino and alpha-keto acid profiles and ROS production.
The aim of this study was to determine the effects of alpha-ketoglutarate on neutrophil (PMN), free alpha-keto and amino-acid profiles as well as important reactive oxygen species (ROS) produced [superoxide anion (O(2) (-)), hydrogen peroxide (H(2)O(2))] and released myeloperoxidase (MPO) activity. Exogenous alpha-ketoglutarate significantly increased PMN alpha-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 alpha-ketoglutarate changes, increases in O(2) (-) formation, H(2)O(2)-generation and MPO activity have also been observed. We therefore believe that alpha-ketoglutarate is important for affecting PMN "susceptible free amino- and alpha-keto acid pools" although important mechanisms and backgrounds are not yet completely explored. Moreover, our results also show very clearly that changes in intragranulocytic alpha-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.
Mühling
Jörg
J
Clinics of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Giessen and Marburg GmbH, Justus-Liebig-University Giessen, Giessen, Germany. joerg.muehling@chiru.med.uni-giessen.de
Tussing
F
F
Nickolaus
K A
KA
Matejec
R
R
Henrich
M
M
Harbach
H
H
Wolff
M
M
Weismüller
K
K
Engel
J
J
Welters
I D
ID
Langefeld
T W
TW
Fuchs
M
M
Weigand
M A
MA
Heidt
M C
MC
D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007651:Keto Acids / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D055815:Young Adult
D000596:Amino Acids; D007651:Keto Acids; D007656:Ketoglutaric Acids; D017382:Reactive Oxygen Species