Xanthurenic Acid Inhibits Metal Ion-Induced Lipid Peroxidation and Protects NADP-Isocitrate Dehydrogenase from Oxidative Inactivation.

Murakami, Keiko; Ito, Masae; Yoshino, Masataka

doi:10.3177/jnsv.47.306

Cited by 25 publications

(17 citation statements)

References 10 publications

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“…The present findings indicate that quinoline compounds with 8-hydroxyl group such as xanthurenic acid can act as a prooxidant. On the contrary, xanthurenic acid sometimes acts as an antioxidant: our previous study showed that xanthurenic acid inhibits the iron-mediated lipid peroxidation, and protects NADP-isocitrate dehydrogenase by chelating iron and copper (Murakami & Yoshino 2001). However, formation of metal-chelate complex modifying the oxidation-reduction potential of metal ion is responsible for the generation of reactive oxygen species (Welch et al 2002).…”

Section: Discussionmentioning

confidence: 96%

Prooxidant action of xanthurenic acid and quinoline compounds: Role of transition metals in the generation of reactive oxygen species and enhanced formation of 8-hydroxy-2′-deoxyguanosine in DNA†

2006

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Xanthurenic acid, a product of tryptophan-NAD pathway, and quinoline compounds produced reactive oxygen species as a complex with iron. Aconitase, the most sensitive enzyme to oxidative stress was inactivated effectively by xanthurenic acid and to a lesser extent by 8-quinolinol in the presence of ferrous sulfate. The inactivation of aconitase was iron-dependent, and was prevented by TEMPOL, a scavenger of reactive oxygen species, suggesting that reduced iron bound to xanthurenic acid or 8-quinolinol can activate oxygen molecule to form superoxide radical. However, kynurenic acid and quinaldic acid without 8-hydroxyl group did not produce reactive oxygen species. Of the quinoline compounds tested, xanthurenic acid and 8-quinolinol with 8-hydroxyl group stimulated the autooxidation of ferrous ion, but kynurenic acid and quinaldic acid did not affect the oxidation of ferrous ion. Hydroxyl group at 8-positions of quinoline compounds was essential for the binding of iron causing the generation of reactive oxygen species. 8-Quinolinol effectively enhanced the ascorbate/copper-mediated formation of 8-hydroxy-2¢-deoxyguanosine in DNA, suggesting the quinolinol/copper-dependent stimulation hydroxyl radical formation. Xanthurenic acid and 8-quinolinol as the metal-chelate complexes can show various cytotoxic effects by generating reactive oxygen species through the ferrous or cuprous ion-dependent activation of oxygen molecule.

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Section: Discussionmentioning

confidence: 96%

Prooxidant action of xanthurenic acid and quinoline compounds: Role of transition metals in the generation of reactive oxygen species and enhanced formation of 8-hydroxy-2′-deoxyguanosine in DNA†

2006

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“…Some groups have shown that XA has metal-chelating activities and antioxidant properties(138, 141, 142). In the 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) system, XA is an efficient scavenger of hydroxyl radicals and ABTS ·+ .…”

Section: Kynurenine Pathwaymentioning

confidence: 99%

“…In the 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) system, XA is an efficient scavenger of hydroxyl radicals and ABTS ·+ . It can inhibit iron- and copper oxidation-induced lipid peroxidation in low-density lipoproteins (LDL) in a pH-dependent manner(141, 142). Moreover, XA prevents the inactivation of NADP + -isocitrate dehydrogenase that is induced by the oxidation of these metals(141).…”

Section: Kynurenine Pathwaymentioning

confidence: 99%

“…It can inhibit iron- and copper oxidation-induced lipid peroxidation in low-density lipoproteins (LDL) in a pH-dependent manner(141, 142). Moreover, XA prevents the inactivation of NADP + -isocitrate dehydrogenase that is induced by the oxidation of these metals(141). XA scavenges superoxide in a hematoxylin autooxidation system(34) and acts as a peroxyl radical scavenger in vitro (138).…”

Section: Kynurenine Pathwaymentioning

confidence: 99%

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Tryptophan-kynurenine pathway is dysregulated in inflammation and immune activation

Liu²,

et al. 2015

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The kynurenine (Kyn) pathway is the major route for tryptophan (Trp) metabolism, and it contributes to several fundamental biological processes. Trp is constitutively oxidized by tryptophan 2, 3-dioxygenase in liver cells. In other cell types, it is catalyzed by an alternative inducible indoleamine-pyrrole 2, 3-dioxygenase (IDO) under certain pathophysiological conditions, which consequently increases the formation of Kyn metabolites. IDO is up-regulated in response to inflammatory conditions as a novel marker of immune activation in early atherosclerosis. Besides, IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis. In particular, Kyn, 3-hydroxykynurenine, and quinolinic acid are positively associated with inflammation, oxidative stress (SOX), endothelial dysfunction, and carotid artery intima-media thickness values in end-stage renal disease patients. Moreover, IDO is a potential novel contributor to vessel relaxation and metabolism in systemic infections, which is also activated in acute severe heart attacks. The Kyn pathway plays a key role in the increased prevalence of cardiovascular disease by regulating inflammation, SOX, and immune activation.

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“…Notably, however, recent studies have also begun to indicate a physiological role of the metabolite in mammals. Thus, XA, which exhibits antioxidant properties both in vitro and in vivo (Christen et al, 1990, Murakami et al, 2001, Lima et al, 2012), has vasorelaxing properties (Fazio et al, 2017a), attenuates tetrahydrobiopterine biosynthesis (Haruki et al, 2016) and may regulate glucose homeostasis (Favennec et al, 2016). Notably, XA induces apoptotic cell death in cultured lens epithelial cells (Malina et al, 2002) and has been repeatedly linked to various pathological events, including type 2 diabetes (Oxenkrug, 2015).…”

Section: Introductionmentioning

confidence: 99%

Xanthurenic Acid Formation from 3-Hydroxykynurenine in the Mammalian Brain: Neurochemical Characterization and Physiological Effects

Sathyasaikumar

Tararina

et al. 2017

Neuroscience

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Xanthurenic acid (XA), formed from 3-hydroxykynurenine (3-HK) in the kynurenine pathway of tryptophan degradation, may modulate glutamatergic neurotransmission by inhibiting the vesicular glutamate transporter and/or activating Group II metabotropic glutamate receptors. Here we examined the molecular and cellular mechanisms by which 3-HK controls the neosynthesis of XA in rat, mouse and human brain, and compared the physiological actions of 3-HK and XA in the rat brain. In tissue homogenates, XA formation from 3-HK was observed in all three species and traced to a major role of kynurenine aminotransferase II (KAT II). Transamination of 3-HK to XA was also demonstrated using human recombinant KAT II. Neosynthesis of XA was significantly increased in the quinolinate-lesioned rat striatum, indicating a non-neuronal localization of the process. Studies using rat cortical slices revealed that newly produced XA is rapidly released into the extracellular compartment, and that XA biosynthesis can be manipulated experimentally in the same way as the production of kynurenic acid from kynurenine (omission of Na+ or glucose, depolarizing conditions, or addition of 2-oxoacids). The synthesis of XA from 3-HK was confirmed in vivo by striatal microdialysis. In slices from the rat hippocampus, both 3-HK and XA reduced the slopes of dentate gyrus field EPSPs. The effect of 3-HK was reduced in the presence of the KAT inhibitor aminooxyacetic acid. Finally, both 3-HK and XA reduced the power of gamma-oscillatory activity recorded from the hippocampal CA3 region. Endogenous XA, newly formed from 3-HK, may therefore play a physiological role in attentional and cognitive processes.

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Xanthurenic Acid Inhibits Metal Ion-Induced Lipid Peroxidation and Protects NADP-Isocitrate Dehydrogenase from Oxidative Inactivation.

Cited by 25 publications

References 10 publications

Prooxidant action of xanthurenic acid and quinoline compounds: Role of transition metals in the generation of reactive oxygen species and enhanced formation of 8-hydroxy-2′-deoxyguanosine in DNA†

Prooxidant action of xanthurenic acid and quinoline compounds: Role of transition metals in the generation of reactive oxygen species and enhanced formation of 8-hydroxy-2′-deoxyguanosine in DNA†

Tryptophan-kynurenine pathway is dysregulated in inflammation and immune activation

Xanthurenic Acid Formation from 3-Hydroxykynurenine in the Mammalian Brain: Neurochemical Characterization and Physiological Effects

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