Effects of kynurenine metabolites on mesangial cell proliferation and gene expression

Yoshimura, Hiromitsu; Sakai, Takayuki; Kuwahara, Yusuke; Ito, Masayoshi; Tsuritani, Katsuki; Hirasawa, Yasushi; Nagamatsu, Tadashi

doi:10.1016/j.yexmp.2009.02.002

Cited by 26 publications

(27 citation statements)

References 27 publications

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“…Quinolinate has been known to associate with various disease conditions, such as infection and neurodegenerative disease (reviewed in Schwarcz, 2004). Interestingly, one recent study further suggested a link between quinolinate and kidney disease (Yoshimura et al, 2009), with similar findings of increased proliferation when kidney mesangial cell were exposed to this compound in vitro, similar to what was observed in RCC cell lines in the present study. The mechanism of its deleterious (and potentially oncogenic) effect is not fully understood, although it has been proposed that quinolinate can induce oxidative stress through iron-catalyzed Fenton reactions (Stone et al, 2007).…”

Section: Discussionsupporting

confidence: 88%

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Urine Metabolomic Analysis Identifies Potential Biomarkers and Pathogenic Pathways in Kidney Cancer

Kim

Taylor

Ganti

et al. 2011

OMICS: A Journal of Integrative Biology

137

111

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Kidney cancer is the seventh most common cancer in the Western world, its incidence is increasing, and it is frequently metastatic at presentation, at which stage patient survival statistics are grim. In addition, there are no useful biofluid markers for this disease, such that diagnosis is dependent on imaging techniques that are not generally used for screening. In the present study, we use metabolomics techniques to identify metabolites in kidney cancer patients' urine, which appear at different levels (when normalized to account for urine volume and concentration) from the same metabolites in nonkidney cancer patients. We found that quinolinate, 4-hydroxybenzoate, and gentisate are differentially expressed at a false discovery rate of 0.26, and these metabolites are involved in common pathways of specific amino acid and energetic metabolism, consistent with high tumor protein breakdown and utilization, and the Warburg effect. When added to four different (three kidney cancer-derived and one ''normal'') cell lines, several of the significantly altered metabolites, quinolinate, aketoglutarate, and gentisate, showed increased or unchanged cell proliferation that was cell line-dependent. Further evaluation of the global metabolomics analysis, as well as confirmation of the specific potential biomarkers using a larger sample size, will lead to new avenues of kidney cancer diagnosis and therapy.

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Section: Discussionsupporting

confidence: 88%

“…When added at physiologic (Grootveld and Halliwell, 1986;Wagner et al, 2010;Yoshimura et al, 2009) or supraphysiologic doses to four distinct RCC cell lines, all three of these metabolites resulted in increased or unchanged cell proliferation (Fig. 3a-c).…”

Section: Experimental Validation Of Individual Metabolitesmentioning

confidence: 99%

Urine Metabolomic Analysis Identifies Potential Biomarkers and Pathogenic Pathways in Kidney Cancer

Kim

Taylor

Ganti

et al. 2011

OMICS: A Journal of Integrative Biology

137

111

View full text Add to dashboard Cite

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“…Furthermore, it was demonstrated in mesangial cell culture experiments that kynurenine stimulates profibrotic gene expression [23]. The authors concluded that kynurenine metabolites might be associated with the progression of glomerular fibrosis and renal failure [23]. Such observations indicate a possible pathological role of accumulated kynurenine metabolites in the progression of renal failure and might also serve as one possible explanation for the association between elevated plasma kynurenine and an increased risk of MAKE in this study [23].…”

Section: Discussionmentioning

confidence: 60%

“…Interestingly, kynurenine formamidase knock out animals display a significant increase of metabolites of the kynurenine pathway, concomitant to a gradual deterioration of kidney function [22]. Furthermore, it was demonstrated in mesangial cell culture experiments that kynurenine stimulates profibrotic gene expression [23]. The authors concluded that kynurenine metabolites might be associated with the progression of glomerular fibrosis and renal failure [23].…”

Section: Discussionmentioning

confidence: 99%

“…It was demonstrated that CKD patients display increased kynurenine plasma levels [19-21]. Furthermore, it was shown in animal and cell culture experiments that kynurenine does not just accumulate in CKD patients due to impaired kidney function, but that the kynurenine pathway might be involved in the pathogenesis of CKD [22, 23]. Given the current evidence, kynurenine might serve as a new biomarker to assess the risk of kidney disease [18-21].…”

Section: Introductionmentioning

confidence: 99%

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Pre-Interventional Kynurenine Predicts Medium-Term Outcome after Contrast Media Exposure Due to Coronary Angiography

Reichetzeder

Heunisch

Einem

et al. 2017

Kidney Blood Press Res

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Background/Aims: Contrast induced acute kidney injury (CI-AKI) remains a serious complication of contrast media enhanced procedures like coronary angiography. There is still a lack of established biomarkers that help to identify patients at high risk for short and long-term complications. The aim of the current study was to evaluate plasma kynurenine as a predictive biomarker for CI-AKI and long-term complications, measured by the combined endpoint "major adverse kidney events" (MAKE) up to 120 days after CM application. Methods: In this prospective cohort study 245 patients undergoing coronary angiography were analyzed. Blood samples were obtained at baseline, 24h and 48h after contrast media (CM) application to diagnose CI-AKI. Patients were followed for 120 days for adverse clinical events including death, the need for dialysis, and a doubling of plasma creatinine. Occurrence of any of these events was summarized in the combined endpoint MAKE. Results: Preinterventional plasma kynurenine was not associated with CI-AKI. Patients who later developed MAKE displayed significantly increased preinterventional plasma kynurenine levels (p<0.0001). ROC analysis revealed that preinterventional kynurenine is highly predictive for MAKE (AUC=0.838; p<0.0001). The optimal cutoff was found at ≥3.5 µmol/L Using this cutoff, the Kaplan-Meier estimator demonstrated that concentrations of plasma kynurenine ≥3.5 µmol/L were significantly associated with a higher prevalence of MAKE until follow up (p<0.0001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. Conclusion: Preinterventional plasma kynurenine might serve as a highly predictive biomarker for MAKE up to 120 days after coronary angiography.

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The Function of Tryptophan Metabolism in the Gut

Tang,

Li,

Gao

et al. 2024

Tryptophan in Animal Nutrition and Human Health

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Effects of kynurenine metabolites on mesangial cell proliferation and gene expression

Cited by 26 publications

References 27 publications

Urine Metabolomic Analysis Identifies Potential Biomarkers and Pathogenic Pathways in Kidney Cancer

Urine Metabolomic Analysis Identifies Potential Biomarkers and Pathogenic Pathways in Kidney Cancer

Pre-Interventional Kynurenine Predicts Medium-Term Outcome after Contrast Media Exposure Due to Coronary Angiography

The Function of Tryptophan Metabolism in the Gut

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