l-Cysteine sulphinate, endogenous sulphur-containing amino acid, inhibits rat brain kynurenic acid production via selective interference with kynurenine aminotransferase II

Kocki, Tomasz; Luchowski, Piotr; Luchowska, Elzbieta; Wielosz, Marian; Turski, Waldemar A.; Urbańska, Ewa M.

doi:10.1016/s0304-3940(03)00579-2

Cited by 49 publications

(34 citation statements)

References 19 publications

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“…For comparison, L-and Dhomocysteic acid had no influence on KYNA production up to 1 mM under the same conditions. It seems, that the observed effect can be mediated via the interaction with KATs intracellularly, since glutamate and D,L-homocysteine were found to inhibit both KYNA biosynthetic enzymes (34,35).…”

Section: Discussionmentioning

confidence: 99%

Demonstration of Kynurenine Aminotransferases I and II and Characterization of Kynurenic Acid Synthesis in Oligodendrocyte Cell Line (OLN-93)

et al. 2005

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In the present study we demonstrate for the first time that both kynurenine aminotransferase (KAT) isoforms I and II are present in the permanent immature rat oligodendrocytes cell line (OLN-93). Moreover, we provide evidence that OLN-93 cells are able to synthesize kynurenic acid (KYNA) from exogenously added L-kynurenine and we characterize its regulation by extrinsic factors. KYNA production in OLN-93 cells was depressed in the presence of aminotransferase inhibitor, aminooxyacetic acid and was not affected by depolarizing agents such as 50 mM K+ and 4-aminopyridine. Glutamate agonists, L-glutamate and D,L-homocysteine significantly decreased KYNA production. Selective agonist of ionotropic glutamate receptors Amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropionic acid (AMPA) lowered KYNA production in OLN-93 cell line, whereas N-methyl-D-aspartate (NMDA) had no influence on KYNA production. Furthermore, KYNA synthesis in OLN-93 cells was decreased in a concentration-dependent manner by amino acids transported by L-system, L-leucine, L-cysteine and L-tryptophan. The role of KYNA synthesis in oligodendrocytes needs further investigation.

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Section: Discussionmentioning

confidence: 99%

Demonstration of Kynurenine Aminotransferases I and II and Characterization of Kynurenic Acid Synthesis in Oligodendrocyte Cell Line (OLN-93)

et al. 2005

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“…5). Notably, KYNA synthesis in the brain is subject to rapid up-or down-regulation by several mechanisms including seizure activity (Wu and Schwarcz 1996), depolarizing agents such as veratridine or potassium (Turski et al 1989;Wu et al 1992), cellular energy status (Hodgkins and Schwarcz 1998), 2-oxoacid availability (Hodgkins et al 1999), dopaminergic drugs (Poeggeler et al 1998) and relatively uncommon endogenous amino acids such as L-a-aminoadipate (Wu et al 1995) and cysteine sulfinate (Kocki et al 2003). Of possible importance in the context of Fig.…”

Section: Discussionmentioning

confidence: 99%

Neuronal A₁ receptors mediate increase in extracellular kynurenic acid after local intrastriatal adenosine infusion

Fuxé

Schwarcz

2004

Journal of Neurochemistry

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The naturally occurring purine nucleoside adenosine has pronounced anticonvulsant and neuroprotective properties and plays a neuromodulatory role in the CNS. Kynurenic acid (KYNA) is an astrocyte-derived, endogenous neuroinhibitory compound, which shares several of adenosine's properties. In a first attempt to examine possible interactions between these two biologically active molecules, adenosine was focally applied into the striatum of freely moving rats by reverse microdialysis, and changes in extracellular KYNA were monitored over time. A 2-h infusion of adenosine increased KYNA levels in a dose-dependent manner, with 10 mM of adenosine causing a twofold elevation within 1 h. This effect was reversible and was effectively blocked by coinfusion of the specific A 1 adenosine receptor antagonist 8-cyclopentyltheophylline (100 lM). In contrast, coinfusion of adenosine with MSX-3 (100 lM), an A 2A receptor antagonist, did not affect the adenosine-induced increase in KYNA levels. Local striatal perfusion with the A 1 receptor agonist N 6 -cyclopentyladenosine (100 lM) mimicked the effect of adenosine, whereas perfusion with the A 2A receptor agonist CGS-21680 (100 lM) was ineffective. Finally, we tested the effect of adenosine (10 mM) on extracellular KYNA in striata that had been injected with quinolinate (60 nmol/1 lL) 7 days earlier. In this neuron-depleted tissue, perfusion with adenosine failed to affect extracellular KYNA levels. These data demonstrate that adenosine is capable of raising extracellular KYNA in the rat striatum by interacting with postsynaptic neuronal A 1 receptors. This mechanism may result in a synergism between the neurobiological effects of adenosine and KYNA.

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“…The activities of KAT I and KAT II were assayed in naïve set of animals, as described before (Kocki et al 2003). Briefly, freshly obtained cortical brain tissue (whole cortices) was homogenized (1:9; wt:vol) in 5 mM Tris-acetate buffer, pH 8.0, containing 50 lM pyridoxal-5 0 -phosphate and 10 mM 2-mercaptoethanol.…”

Section: Semi-purified Cortical Homogenatementioning

confidence: 99%

“…A number of endogenous and exogenous factors influencing the central production of KYNA have been recognized. For example, mitochondrial toxins compromising the status of mitochondrial respiration, endogenous sulfur-containing amino acids and inhibitors of protein kinase A activity reduce formation of KYNA, whereas rise of intracellular cAMP level stimulates KYNA production (Urbanska et al 1997;Luchowski et al 2002;Kocki et al 2003;Luchowska et al 2005Luchowska et al , 2009Kloc et al 2008). It was also shown that hyperglycemia enhances the inhibitory effect of mitochondrial toxins and D,L-homocysteine on the central production of KYNA (Chmiel-Perzyńska et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Novel Aspect of Ketone Action: β-Hydroxybutyrate Increases Brain Synthesis of Kynurenic Acid In Vitro

et al. 2010

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Ketone bodies formed during ketogenic diet or non-treated diabetes mellitus may exert neuroprotective and antiepileptic effects. Here, we assessed the influence of ketone body, β-hydroxybutyrate (BHB) on the brain synthesis of kynurenic acid (KYNA), an endogenous antagonist of glutamatergic and α7-nicotinic receptors. In brain cortical slices and in primary glial cultures, BHB enhanced KYNA production. KT 5270, an inhibitor of protein kinase A, has prevented this action. At hypoglycemia, under pH 7.0 and 7.4, profound (15 mM BHB), but not mild (3 mM) ketosis increased synthesis of KYNA. In paradigm resembling diabetic ketoacidosis in vitro (30 mM glucose, pH 7.0), neither mild nor profound ketosis influenced the production of KYNA. At pH 7.4 and in 30 mM glucose though, both mild and severe ketonemia evoked an increase of KYNA production. The activity of KYNA biosynthetic enzymes, KAT I and KAT II, in cortical homogenate was not altered by BHB (0.05-10.0 mM). However, in cultured glial cells exposed to BHB (10 mM), the activity of KATs increased. This effect was reversed by the co-incubation of cells with KT 5270. Presented data reveal a novel mechanism of action of BHB. Increased synthesis of KYNA in the presence of BHB is most probably mediated by protein kinase A-dependent stimulation of KATs expression/activity leading to an increase of KYNA formation. Ensuing attenuation of the excessive excitatory glutamate-mediated neurotransmission may, at least in part, explain the neuroprotective actions of BHB.

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l-Cysteine sulphinate, endogenous sulphur-containing amino acid, inhibits rat brain kynurenic acid production via selective interference with kynurenine aminotransferase II

Cited by 49 publications

References 19 publications

Demonstration of Kynurenine Aminotransferases I and II and Characterization of Kynurenic Acid Synthesis in Oligodendrocyte Cell Line (OLN-93)

Demonstration of Kynurenine Aminotransferases I and II and Characterization of Kynurenic Acid Synthesis in Oligodendrocyte Cell Line (OLN-93)

Neuronal A₁ receptors mediate increase in extracellular kynurenic acid after local intrastriatal adenosine infusion

Novel Aspect of Ketone Action: β-Hydroxybutyrate Increases Brain Synthesis of Kynurenic Acid In Vitro

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l-Cysteine sulphinate, endogenous sulphur-containing amino acid, inhibits rat brain kynurenic acid production via selective interference with kynurenine aminotransferase II

Cited by 49 publications

References 19 publications

Demonstration of Kynurenine Aminotransferases I and II and Characterization of Kynurenic Acid Synthesis in Oligodendrocyte Cell Line (OLN-93)

Demonstration of Kynurenine Aminotransferases I and II and Characterization of Kynurenic Acid Synthesis in Oligodendrocyte Cell Line (OLN-93)

Neuronal A1 receptors mediate increase in extracellular kynurenic acid after local intrastriatal adenosine infusion

Novel Aspect of Ketone Action: β-Hydroxybutyrate Increases Brain Synthesis of Kynurenic Acid In Vitro

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Neuronal A₁ receptors mediate increase in extracellular kynurenic acid after local intrastriatal adenosine infusion