Evidence map›Paper›PMID 25650382›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2015

Quantitative profiling of human renal UDP-glucuronosyltransferases and glucuronidation activity: a comparison of normal and tumoral kidney tissues.

Guillaume Margaillan, Michèle Rouleau, John K Fallon, Patrick Caron, Lyne Villeneuve, Véronique Turcotte, Philip C Smith, Melanie S Joy, Chantal Guillemette

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
13.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 88 citations in OpenAlex.

  1. Trial
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  3. Stereoselective Glucuronidation of Bupropion Metabolites In Vitro and In Vivo.Drug metabolism and disposition: the biological fate of chemicals · 2016
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  16. Inhibition of UDP-Glucuronosyltransferase Enzymes by Major Cannabinoids and Their Metabolites.Drug metabolism and disposition: the biological fate of chemicals · 2021
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Guillaume MargaillanPharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center, and Faculty of Pharmacy, Laval University, Quebec, Canada (G.M., M.R., P.C., L.V., V.T., C.G.); Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); and University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Boulder, Colorado (M.S.J.).
Michèle RouleauPharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center, and Faculty of Pharmacy, Laval University, Quebec, Canada (G.M., M.R., P.C., L.V., V.T., C.G.); Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); and University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Boulder, Colorado (M.S.J.).
John K FallonPharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center, and Faculty of Pharmacy, Laval University, Quebec, Canada (G.M., M.R., P.C., L.V., V.T., C.G.); Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); and University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Boulder, Colorado (M.S.J.).
Patrick CaronPharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center, and Faculty of Pharmacy, Laval University, Quebec, Canada (G.M., M.R., P.C., L.V., V.T., C.G.); Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); and University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Boulder, Colorado (M.S.J.).
Lyne VilleneuvePharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center, and Faculty of Pharmacy, Laval University, Quebec, Canada (G.M., M.R., P.C., L.V., V.T., C.G.); Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); and University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Boulder, Colorado (M.S.J.).
Véronique TurcottePharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center, and Faculty of Pharmacy, Laval University, Quebec, Canada (G.M., M.R., P.C., L.V., V.T., C.G.); Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); and University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Boulder, Colorado (M.S.J.).
Philip C SmithPharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center, and Faculty of Pharmacy, Laval University, Quebec, Canada (G.M., M.R., P.C., L.V., V.T., C.G.); Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); and University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Boulder, Colorado (M.S.J.).
Melanie S JoyPharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center, and Faculty of Pharmacy, Laval University, Quebec, Canada (G.M., M.R., P.C., L.V., V.T., C.G.); Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); and University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Boulder, Colorado (M.S.J.).
Chantal GuillemettePharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center, and Faculty of Pharmacy, Laval University, Quebec, Canada (G.M., M.R., P.C., L.V., V.T., C.G.); Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); and University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Boulder, Colorado (M.S.J.) chantal.guillemette@crchudequebec.ulaval.ca.
University of North Carolina at Chapel Hill · USUniversity of Colorado Anschutz Medical Campus · USCentre hospitalier universitaire de Québec · CAUniversity of Montana · US

Funding

Shared UPLC-MS/MS for Absolute Quantitative ProteomicsS10RR024595 · NCRR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SMITH, PHILIP C · 2008 to 2008
$381k
Canadian Institutes of Health Research MOP-42392NCRR NIH HHS S10 RR024595NCRR NIH HHS S10-RR024595
6 · The paper itself

Abstract

Renal metabolism by UDP-glucuronosyltransferase (UGT) enzymes is central to the clearance of many drugs. However, significant discrepancies about the relative abundance and activity of individual UGT enzymes in the normal kidney prevail among reports, whereas glucuronidation in tumoral kidney has not been examined. In this study, we performed an extensive profiling of glucuronidation metabolism in normal (n = 12) and tumor (n = 14) kidneys using targeted mass spectrometry quantification of human UGTs. We then correlated UGT protein concentrations with mRNA levels assessed by quantitative polymerase chain reaction and with conjugation activity for the major renal UGTs. Beyond the wide interindividual variability in expression levels observed among kidney samples, UGT1A9, UGT2B7, and UGT1A6 are the most abundant renal UGTs in both normal and tumoral tissues based on protein quantification. In normal kidney tissues, only UGT1A9 protein levels correlated with mRNA levels, whereas UGT1A6, UGT1A9, and UGT2B7 quantification correlated significantly with their mRNA levels in tumor kidneys. Data support that posttranscriptional regulation of UGT2B7 and UGT1A6 expression is modulating glucuronidation in the kidney. Importantly, our study reveals a significant decreased glucuronidation capacity of neoplastic kidneys versus normal kidneys that is paralleled by drastically reduced UGT1A9 and UGT2B7 mRNA and protein expression. UGT2B7 activity is the most repressed in tumors relative to normal tissues, with a 96-fold decrease in zidovudine metabolism, whereas propofol and sorafenib glucuronidation is decreased by 7.6- and 5.2-fold, respectively. Findings demonstrate that renal drug metabolism is predominantly mediated by UGT1A9 and UGT2B7 and is greatly reduced in kidney tumors.

Indexed as

Carcinoma, Renal CellGlucuronidesGlucuronosyltransferaseHumansKidneyKidney NeoplasmsPharmaceutical PreparationsReal-Time Polymerase Chain ReactionRNA, MessengerUDP-Glucuronosyltransferase 1A9GlucuronidesGlucuronosyltransferasePharmaceutical PreparationsRNA, MessengerUDP-Glucuronosyltransferase 1A9UDP-glucuronosyltransferase, UGT1A6UGT1A9 protein, humanUGT2B7 protein, human

Identifiers

PMID25650382
PMCPMC4366751
OpenAlexW2158774304

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.