Kidney and Liver Kynurenine Pathway Enzymes in Chronic Renal Failure

Tankiewicz, A; Pawlak, Dariusz; Topczewska-Bruns, J.; Buczko, Włodzimierz

doi:10.1007/978-1-4615-0135-0_48

Cited by 24 publications

(24 citation statements)

References 19 publications

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“…Hydroxykynurenine is part of the kynurenine pathway and generated as a result of tryptophan degradation [57]. Increased plasma levels of hydroxykynurenine have previously been reported to be associated with advanced stage CKD [58], [59].…”

Section: Discussionmentioning

confidence: 99%

Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

Nkuipou‐Kenfack

Duranton²,

Gayrard³

et al. 2014

PLoS ONE

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Chronic kidney disease (CKD) is part of a number of systemic and renal diseases and may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis and management of CKD. We hypothesised that combining metabolomic and proteomic approaches could generate a more systemic and complete view of the disease mechanisms. To test this approach, we examined samples from a cohort of 49 patients representing different stages of CKD. Urine samples were analysed for proteomic changes using capillary electrophoresis-mass spectrometry and urine and plasma samples for metabolomic changes using different mass spectrometry-based techniques. The training set included 20 CKD patients selected according to their estimated glomerular filtration rate (eGFR) at mild (59.9±16.5 mL/min/1.73 m2; n = 10) or advanced (8.9±4.5 mL/min/1.73 m2; n = 10) CKD and the remaining 29 patients left for the test set. We identified a panel of 76 statistically significant metabolites and peptides that correlated with CKD in the training set. We combined these biomarkers in different classifiers and then performed correlation analyses with eGFR at baseline and follow-up after 2.8±0.8 years in the test set. A solely plasma metabolite biomarker-based classifier significantly correlated with the loss of kidney function in the test set at baseline and follow-up (ρ = −0.8031; p<0.0001 and ρ = −0.6009; p = 0.0019, respectively). Similarly, a urinary metabolite biomarker-based classifier did reveal significant association to kidney function (ρ = −0.6557; p = 0.0001 and ρ = −0.6574; p = 0.0005). A classifier utilising 46 identified urinary peptide biomarkers performed statistically equivalent to the urinary and plasma metabolite classifier (ρ = −0.7752; p<0.0001 and ρ = −0.8400; p<0.0001). The combination of both urinary proteomic and urinary and plasma metabolic biomarkers did not improve the correlation with eGFR. In conclusion, we found excellent association of plasma and urinary metabolites and urinary peptides with kidney function, and disease progression, but no added value in combining the different biomarkers data.

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Section: Discussionmentioning

confidence: 99%

Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

Nkuipou‐Kenfack

Duranton²,

Gayrard³

et al. 2014

PLoS ONE

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“…Moreover, a direct correlation between IDO silencing and Fas-mediated cell death has been observed in several tumor cell lines (19). Our previous work has demonstrated that stimulation of TEC with IFN-␥ and TNF-␣ results in increased Fas expression and a Fas/FasLdependent form of self-injury or fratricide (10), and others have suggested that Fas/FasL interaction within the kidney may be harmful (4,11,26,34,35,38). Given that both Fas and IDO are induced by IFN-␥ and TNF-␣, we tested the potential proapoptotic capacity of IDO in this Fas-mediated TEC fratricide.…”

Section: Upregulation Of Ido Expression and Activity In Tec In Responmentioning

confidence: 95%

“…IDO expression has been previously observed in the kidney (8,19,30) and thus suggested to play an important role in acute rejection and chronic renal failure (6,35,38). However, expression by renal tubular epithelium and the precise physiological function of this enzyme, particularly in the pathogenesis of Fas-mediated renal cell apoptosis, has not been investigated.…”

mentioning

confidence: 95%

Proapoptotic activity of indoleamine 2,3-dioxygenase expressed in renal tubular epithelial cells

Mohib¹,

Guan²,

Diao³

et al. 2007

American Journal of Physiology-Renal Physiology

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Exposure of renal tubular epithelial cells (TEC) to IFN-gamma/TNF-alpha leads to Fas/FasL-mediated self-injury, which contributes to allograft rejection. Indoleamine 2,3-dioxygenase (IDO) converts tryptophan to N-formyl-kynurenine and contributes to immune privilege in tissues by increasing Fas-mediated T cell apoptosis. However, renal expression of IDO and its role in promoting Fas-mediated TEC death have not been examined. IDO expression was analyzed by RT-PCR and Western blot. Apoptosis was measured by fluorescence-activated cell sorting analysis and terminal deoxytransferase-mediated dUTP nick end labeling. We demonstrated that functional IDO is expressed in TEC and is increased by IFN-gamma/TNF-alpha exposure. Increased IDO activity promoted TEC apoptosis, whereas inhibition of IDO by its specific inhibitor 1-methyl-d-tryptophan attenuated IFN-gamma/TNF-alpha-mediated TEC apoptosis and augmented TEC survival. Transgenic expression of IDO resulted in increased TEC apoptosis in the absence of proinflammatory cytokine exposure, supporting a central role for IDO in TEC injury. Inhibition of IDO-mediated TEC death by a caspase-8-specific inhibitor (Z-IETD-FMK), as well as the absence of an IDO effect in Fas-deficient and FasL-deficient TEC, supports a Fas/FasL-dependent, caspase-8-mediated mechanism for IDO-enhanced TEC death. These data suggest that renal IDO expression may be deleterious during renal inflammation, because it enhances TEC self-injury through Fas/FasL interactions. Thus attenuation of IDO may represent a novel strategy to promote kidney function following ischemia and renal allograft rejection.

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“…In contrast to both IDO enzymes, TDO is highly substrate specific and dioxygenases only L-trp and some trp derivatives. Both IDO enzymes display a wider substrate specificity, catalyzing the dioxygenation of D-trp, tryptamine, and serotonin in addition to those substrates dioxygenated by TDO (7). TDO was initially discovered in the 1930s, and its expression is normally restricted to mammalian liver cells where it is believed to regulate systemic trp concentrations (8).…”

Section: Tryptophan and Its Degradation Pathways: Indoleamine 23-diomentioning

confidence: 99%

The indoleamine 2,3‐dioxygenase (IDO) pathway controls allergy

Bubnoff

Bieber

2012

Allergy

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A series of recent studies have demonstrated that the immunoregulatory pathway of tryptophan catabolism, initiated by the enzyme indoleamine 2,3-dioxygenase (IDO), is a critical participant in allergic inflammation. Originally known for its regulatory function during pregnancy and during chronic inflammation in tumorigenesis and infection, the activity of IDO seems to positively modify the inflammatory state of atopy or allergy. The tryptophan degradation pathway is important for tolerance induction during systemic allergen immunotherapy. Here, we focus on recent findings that establish the IDO pathway as central to allergic inflammation.The indoleamine 2,3-dioxygenase (IDO) pathway has been found to contribute substantially to the control of allergic inflammation. Traditionally recognized for its immunomodulatory role in infection, pregnancy, autoimmunity, and neoplasia, the effect of IDO on allergy appears to be a another piece of puzzle in the 'hygiene hypothesis'. Early microbial exposure and thus the stimulation of the IDO pathway by distinct Toll-like receptors (TLR) may, together with other immunoregulatory pathways, shape the predisposition to and determine the outcome of allergic inflammation, autoimmunity, and probably other diseases. Current data suggest that a normal induction of IDO activity, which decreases serum tryptophan (trp) levels and increases the levels of trp metabolites, controls the allergic inflammation. The mechanism of IDO-induced tolerance induction can probably be manifold but the induction of regulatory T cells may be a major aspect of the control function over allergic inflammation. This review summarizes the current knowledge on the IDO pathway and its role in regulating immune functions with a focus on allergic diseases.Tryptophan and its degradation pathways: indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase (TDO)As an essential amino acid, tryptophan (trp) is a constituent of proteins. Inadequate dietary intake of trp and other essential amino acids can lead to a negative nitrogen balance and to a loss of muscle mass, brain size, and weight (1). Trp is an essential starting point of two biochemical pathways: (i) the enzyme tryptophan 5-hydroxylase converts trp into 5-hydroxytryptophan, which is subsequently decarboxylized to 5-hydroxytryptamine (5-HT, serotonin), an essential neurotransmitter and vasoconstrictor, and (ii) two atoms of the molecular oxygen are inserted into L-trp to form N-formylkynurenine, the first and rate-limiting step in the kynurenine pathway (Fig. 1) (2, 3). The activation of molecular oxygen and its insertion into trp are catalyzed by three

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Kidney and Liver Kynurenine Pathway Enzymes in Chronic Renal Failure

Cited by 24 publications

References 19 publications

Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

Proapoptotic activity of indoleamine 2,3-dioxygenase expressed in renal tubular epithelial cells

The indoleamine 2,3‐dioxygenase (IDO) pathway controls allergy

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