Endotoxin challenge reduces aconitase activity in myocardial tissue.
Sepsis impairs mitochondrial respiration but the mechanisms responsible are incompletely understood. We propose that Krebs cycle enzymes are inhibited in sepsis, contributing to reduced rates of oxidative phosphorylation.


OBJECTIVE
The activities of Krebs cycle enzymes are decreased in endotoxemia and contribute to reduced rates of oxidative phosphorylation.


METHODS
Adult male rats received an intraperitoneal injection of either endotoxin or saline. Cardiac mitochondria were subsequently isolated and measures of mitochondrial respiration and enzyme activities performed.


RESULTS
By 24h post endotoxin administration, there was a 28% reduction in mitochondrial respiration (P=0.0005) and a 24% reduction in aconitase activity (P=0.001). Functional activity of the electron transport chain was unaffected.


CONCLUSIONS
Our data demonstrate that in the heart, the administration of endotoxin significantly and selectively decreased aconitase activity in association with reduced rates of oxidative phosphorylation. We conclude that decreased activity of aconitase contributes to the endotoxin-stimulated reduction in mitochondrial respiration.
Mason
Katherine E
KE
Division of Pediatric Critical Care, Department of Pediatrics, Case Western Reserve University, Mail Stop 6010, 11100 Euclid Avenue, Cleveland, OH 44120, USA. Katherine.Mason@Case.edu
Stofan
Daniel A
DA
D000154:Aconitate Hydratase / Q000378:metabolism*; D000818:Animals; D001671:Biochemistry / Q000379:methods; D002952:Citric Acid Cycle; D004731:Endotoxins / Q000378:metabolism*; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009206:Myocardium / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
D004731:Endotoxins; D007655:Ketoglutarate Dehydrogenase Complex; D000154:Aconitate Hydratase; D010100:Oxygen