Comparative effects of oxygen on indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway

Dang, Yuhong; Dale, William E.; Brown, Olen R.

doi:10.1016/s0891-5849(99)00272-5

Cited by 67 publications

(42 citation statements)

References 41 publications

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“…Increased expression of Trp-tRNA synthase (WARS) in response to IFN-␥ might compensate for a reduced availability of Trp for protein synthesis resulting from IDO activation. An antiinflammatory role for WARS is also conceivable because the vascular endothelial WARS is proteolytically processed to an anti-angiogenic factor (44,45) Elevated circulating levels of CXCL9, CXCL10, and CXCL11 are reported in type 1 diabetes in human serum (40) and suggest that the response to IFN-␥ seen here in vitro may model a physiologically relevant response. Further information is needed concerning the spatio-temporal pattern of expression of IFN-␥-responsive genes and their modifiers such as IL-4 and IL-4 receptors.…”

Section: Discussionmentioning

confidence: 83%

Induction of Indoleamine 2,3-Dioxygenase by Interferon-γ in Human Islets

et al. 2007

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Section: Discussionmentioning

confidence: 83%

Induction of Indoleamine 2,3-Dioxygenase by Interferon-γ in Human Islets

et al. 2007

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“…Although TRP readily crosses the blood-brain barrier (BBB), levels of IDO1 and TDO2 are much lower in the brain than in the periphery [46]) and thus ~60% of KP metabolism in the brain is initiated by brain penetrant L-KYN synthesized in the periphery [47], which is taken up by glial cells [48]. The two predominant arms of L-KYN metabolism are physically separated in the brain: KMO is expressed in microglia but not in astrocytes, thus the 3-HK arm of the pathway leading to QUIN production, takes place in microglia [45], while KATs are expressed in astrocytes -but not microglia -and therefore production of KYNA within the CNS occurs in astrocytes [49] (Figure 2).…”

Section: Regulation Of the Kynurenine Pathway In The Cns And Peripherymentioning

confidence: 99%

The kynurenine pathway and neurodegenerative disease

Maddison

Giorgini

2015

Seminars in Cell & Developmental Biology

243

223

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Neuroactive metabolites of the kynurenine pathway (KP) of tryptophan degradation have been closely linked to the pathogenesis of several neurodegenerative diseases. Tryptophan is an essential amino acid required for protein synthesis, and in higher eukaryotes is also converted into the key neurotransmitters serotonin and tryptamine. However, in mammals >95% of tryptophan is metabolized through the KP, ultimately leading to the production of nicotinamide adenosine dinucleotide (NAD + ). A number of the pathway metabolites are neuroactive; e.g. can modulate activity of several glutamate receptors and generate/scavenge free radicals. Imbalances in absolute and relative levels of KP metabolites have been strongly associated with neurodegenerative disorders including Huntington's, Alzheimer's, and Parkinson's diseases. The KP has also been implicated in the pathogenesis of other brain disorders (e.g. schizophrenia, bipolar disorder), as well as several cancers and autoimmune disorders such as HIV. Pharmacological and genetic manipulation of the KP has been shown to ameliorate neurodegenerative phenotypes in a number of model organisms, suggesting that it could prove to be a viable target for the treatment of such diseases. Here, we provide an overview of the KP, its role in neurodegeneration and the current strategies for therapeutic targeting of the pathway.

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“…The rate-limiting enzyme of kynurenine formation from tryptophan is the indoleamine 2,3-dioxygenase (IDO) or tryptophan 2,3-dioxygenase (TDO) (Dang et al 2000 ;Oxenkrug 2010a ). Kynurenine is further metabolized in two different pathways, kynurenine-kynurenic acid pathway and kynurenine-nicotinamide adenine dinucleotide (NAD) pathway ( Fig.…”

Section: Tryptophan-kynurenine Pathwaymentioning

confidence: 99%

Diabetes and Tryptophan Metabolism

Ünlütürk

Erbaş

2015

Molecular and Integrative Toxicology

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Tryptophan, an essential amino acid, can be metabolized to several kinds of physiologically active metabolites. Accumulating data indicate that an altered metabolism of tryptophan and its active metabolites have important roles for the pathogenesis and development of complications of diabetes mellitus. Changes in tryptophan-kynurenine and tryptophan-methoxyindole pathways are related to several pathophysiological mechanisms of type 1 or type 2 diabetes. Particularly, serotonin, melatonin, and their receptors would be novel targets not only to better understand the pathogenesis of diabetes but also to develop new antidiabetic agents. Keywords IntroductionIn addition to the traditional knowledge, recent studies show that amino acids are also among the regulators of the phosphorylation cascade of proteins and expression of genes. Moreover, they are crucial precursors of hormones and nitrogenous substances with outstanding biological importance. Even though physiological concentrations of amino acids and their metabolites are necessary for physiological processes, their elevated levels might be pathogenic in several disorders. Several

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Comparative effects of oxygen on indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway

Cited by 67 publications

References 41 publications

Induction of Indoleamine 2,3-Dioxygenase by Interferon-γ in Human Islets

Induction of Indoleamine 2,3-Dioxygenase by Interferon-γ in Human Islets

The kynurenine pathway and neurodegenerative disease

Diabetes and Tryptophan Metabolism

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