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Selected Publication:

Publication type: Journal Article
Document type: Full Paper

Year: 2003

Author(s): Baran, H; Staniek, K; Kepplinger, B; Stur, J; Draxler, M; Nohl, H

Title: Kynurenines and the respiratory parameters on rat heart mitochondria.

Source: Life Sci (72), 10 1103-1115.



Authors Vetmeduni Vienna:

Baran Halina
Nohl Hans
Staniek Katrin

Vetmed Research Units
Institute of Animal Breeding and Genetics
Institute of Animal Nutrition and Functional Plant Compounds
Institute of Pharmacology and Toxicology
Unit of Physiology and Biophysics


Project(s): Kynurenines and the respiratory parameters of rat brain mitochondria: aging and alzheimer s disease


Abstract:
It has been shown recently that the L-kynurenine metabolite kynurenic acid lowers the efficacy of mitochondria ATP synthesis by significantly increasing state IV, and reducing respiratory control index and ADP/oxygen ratio of glutamate/malate-consuming heart mitochondria. In the present study we investigated the effect of L-tryptophan (1.25 microM to 5 mM) and other metabolites of L-kynurenine as 3-hydroxykynurenine (1.25 microM to 2.5 mM), anthranilic acid (1.25 microM to 5 mM) and 3-hydroxyanthranilic acid (1.25 microM to 5 mM) on the heart mitochondria function. Mitochondria were incubated with saturating concentrations of respiratory substrates glutamate/malate (5 mM), succinate (10 mM) or NADH (1 mM) in the presence or absence of L-tryptophan metabolites. Among tested substances, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and anthranilic acid but not tryptophan affected the respiratory parameters dose-dependently, however at a high concentration, of a micro molar range. 3-Hydroxykynurenine and 3-hydroxyanthranilic acid lowered respiratory control index and ADP/oxygen ratio in the presence of glutamate/malate and succinate but not with NADH. While, anthranilic acid reduced state III oxygen consumption rate and lowered the respiratory control index only of glutamate/malate-consuming heart mitochondria. Co-application of anthranilic acid and kynurenic acid (125 or 625 microM each) to glutamate/malate-consuming heart mitochondria caused a non-additive deterioration of the respiratory parameters determined predominantly by kynurenic acid. Accumulated data indicate that within L-tryptophan metabolites kynurenic acid is the most effective, followed by anthranilic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid to influence the respiratory parameters of heart mitochondria. Present data allow to speculate that changes of kynurenic acid and/or anthranilic acid formation in heart tissue mitochondria due to fluctuation of L-kynurenine metabolism may be of functional importance for cardiovascular processes. On the other hand, beside the effect of 3-hydroxyanthranilic acid and 3-hydroxykynurenine on respiratory parameters, their oxidative reactivity may contribute to impairment of mitochondria function, too.

Keywords Pubmed: 3-Hydroxyanthranilic Acid/pharmacology
Animals
Free Radical Scavengers/pharmacology
Kinetics
Kynurenine/analogs & derivatives*
Kynurenine/pharmacology*
Male
Mitochondria, Heart/drug effects
Mitochondria, Heart/metabolism*
Mitochondrial Proteins/metabolism
NAD/metabolism
Oxygen Consumption/drug effects*
Rats
Rats, Sprague-Dawley
Succinates/metabolism
Tryptophan/pharmacology
ortho-Aminobenzoates/pharmacology


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