Kynurenic Acid Inhibits the Release of the Neurotrophic Fibroblast Growth Factor (FGF)-1 and Enhances Proliferation of Glia Cells, in vitro

Serio, Claudia Di; Cozzi, Andrea; Angeli, I; Doria, Laura; Micucci, Isabella; Pellerito, Silvia; Mirone, Patrizia; Masotti, Giulio; Moroni, Flavio; Tarantini, Francesca

doi:10.1007/s10571-005-8469-y

Cited by 48 publications

(35 citation statements)

References 35 publications

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“…A similar effect was previously reported in synoviocytes [16]. In contrast, Di Serio et al [1] reported the stimulatory effect of KYNA on the proliferation rate of mouse microglia and human glioblastoma cells in vitro. Although we investigated the effect of KYNA in a broad range of concentrations from 0.00001 to 10 mM, we did not observe the stimulatory activity of KYNA in HT-29 cells.…”

Section: Resultssupporting

confidence: 82%

Kynurenic acid enhances expression of p21 Waf1/Cip1 in colon cancer HT-29 cells

Walczak

Turski

Rzeski

2012

Pharmacological Reports

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Abstract:Background: Kynurenic acid (KYNA), a tryptophan metabolite, was found in the mucus of rat small intestine. However, its role in the gastrointestinal tract is still not fully elucidated. Methods: To verify whether KYNA affects cell cycle regulators, the protein expression of cyclin-dependent kinase inhibitor p21 Waf1/Cip1 was investigated in colon adenocarcinoma HT-29 cells exposed to KYNA. MTT, BrdU assay and siRNA technology were used to evaluate the effect of KYNA on cancer cell proliferation. Results: KYNA significantly enhanced the expression of p21 Waf1/Cip1. Importantly, the overexpression of this protein was involved in inhibition of proliferation and DNA synthesis in HT-29 cells. Conclusions: KYNA may be considered as a potential chemoprevention agent against colon cancer.

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Section: Resultssupporting

confidence: 82%

Kynurenic acid enhances expression of p21 Waf1/Cip1 in colon cancer HT-29 cells

Walczak

Turski

Rzeski

2012

Pharmacological Reports

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“…It has been shown that QUIN can directly increase proliferation rate of human glioblastoma cell line U343MG (Serio et al, 2005), and we showed here that QUIN can increase SK-N-SH neuroblastoma cell proliferation. Interestingly, QUIN also increases astroglial production of glial cell line-derived neurotrophic factor (Bresjanac and Antauer, 2000), which may induce proliferation of neuroblastoma cells and increase resistance to chemotherapeutic agents (Hansford and Marshall, 2005) (Fig.…”

Section: Discussionsupporting

confidence: 68%

Characterization of the Kynurenine Pathway in Human Neurons

et al. 2007

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The kynurenine pathway is a major route of L-tryptophan catabolism producing neuroactive metabolites implicated in neurodegeneration and immune tolerance. We characterized the kynurenine pathway in human neurons and the human SK-N-SH neuroblastoma cell line and found that the kynurenine pathway enzymes were variably expressed. Picolinic carboxylase was expressed only in primary and some adult neurons but not in SK-N-SH cells. Because of this difference, SK-N-SH cells were able to produce the excitotoxin quinolinic acid, whereas human neurons produced the neuroprotectant picolinic acid. The net result of kynurenine pathway induction in human neurons is therefore predicted to result in neuroprotection, immune regulation, and tumor inhibition, whereas in SK-N-SH cells, it may result in neurotoxicity, immune tolerance, and tumor promotion. This study represents the first comprehensive characterization of the kynurenine pathway in neurons and the first description of the involvement of the kynurenine pathway as a mechanism for controlling both tumor cell neurotoxicity and persistence.

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“…NGF is of special importance because of its regulation of proliferation and subsequent maintenance of cholinergic neurones in the CNS, and hence of relevance to AD and schizophrenia [52]. In contrast, kynurenic acid reduced the release of fibroblast growth factor-1 (FGF-1) in several different experimental models [53], so that its net effects on cell viability may depend on a balance of changes in different growth factors.…”

Section: Growth Factorsmentioning

confidence: 99%

An expanding range of targets for kynurenine metabolites of tryptophan

Stone

Stoy

Darlington

2013

Trends in Pharmacological Sciences

303

207

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The kynurenine pathway of tryptophan metabolism accounts for most of the tryptophan that is not committed to protein synthesis and includes compounds active in the nervous and immune systems. Kynurenine acts on the aryl hydrocarbon receptor, affecting metabolism of xenobiotics and promoting carcinogenesis. Quinolinic acid is an agonist at N-methyl-D-aspartate receptors (NMDAR), but is also pro-oxidant, has immunomodulatory actions and promotes the formation of hyperphosphorylated tau proteins. Kynurenic acid blocks NMDARs and 7-homomeric nicotinic cholinoceptors but is also an agonist at the orphan G-protein-coupled receptor GPR35. 3-hydroxykynurenine and 3-hydroxyanthranilic acid have pronounced redox activity and regulate T cell function. Cinnabarinic acid can activate metabotropic glutamate receptors.The aim of this review is to highlight the increasing range of molecular targets for components of the kynurenine pathway, in both the nervous and immune systems, in relation to their relevance to disease and drug development. 3 The kynurenine pathwayApart from the tryptophan used in protein synthesis, most of this amino acid in mammals is oxidised along the kynurenine pathway. Only around 1% of tryptophan is used for the synthesis of 5-hydroxytrpytamine (5-HT). For many years, most compounds along the pathway ( Figure 1) were thought to have little biological activity until quinolinic acid was shown to be an agonist at glutamate receptors sensitive to NMDA [1] and kynurenic acid was found to be an antagonist at these and other ionotropic glutamate receptors [2]. These two compounds have been the focus of attention on the kynurenine pathway for over 30 years [3,4]. In parallel with work on the central nervous system (CNS), however, there has been growing interest in the role of kynurenines in the immune system, and the last few years have seen the identification of more molecular targets acted on by quinolinic acid, kynurenic acid or other components of the pathway. The key enzymes, indoleamine-2,3-dioxygenase (IDO) and kynurenine-3-monoxygenase (KMO) are also potential drug targets.The aim of this review is to highlight the increasing range of molecular targets now recognised in the nervous and immune systems in relation to their relevance to disease and drug development. Kynurenine metabolites and their receptors in disease Quinolinic acidIn addition to its ability to activate NMDARs selectively, quinolinic acid can generate reactive oxygen species (ROS). This activity can produce substantial oxidation of cellular lipids, especially in the presence of transition metal ions [5]. 4The axon-sparing neuronal loss produced by quinolinic acid in vivo may be due partly to formation of ROS [6] although it certainly also involves activation of NMDARs.Acting on human primary astrocytes, excitotoxic concentrations of quinolinic acid can also promote the expression and secretion of some of the more potent Kynurenic acidTwo early studies of the anti-epileptic actions of kynurenic acid independently reported that i...

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Kynurenic Acid Inhibits the Release of the Neurotrophic Fibroblast Growth Factor (FGF)-1 and Enhances Proliferation of Glia Cells, in vitro

Cited by 48 publications

References 35 publications

Kynurenic acid enhances expression of p21 Waf1/Cip1 in colon cancer HT-29 cells

Kynurenic acid enhances expression of p21 Waf1/Cip1 in colon cancer HT-29 cells

Characterization of the Kynurenine Pathway in Human Neurons

An expanding range of targets for kynurenine metabolites of tryptophan

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