Coexpression of Human Hepatic Uridine Diphosphate Glucuronosyltransferase Proteins: Implications for Ontogenetic Mechanisms and Isoform Coregulation

Uridine diphosphate glucuronosyltransferases (UGTs) catalyze glucuronidation to facilitate systemic and local clearance of numerous chemicals and drugs. To investigate whether UGT expression is coregulated in human liver, we analyzed the protein expression of UGTs 1A1, 1A3, 1A4, 1A6, 1A9, 2B7, 3A1,...

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Veröffentlicht in:Journal of clinical pharmacology 2020-06, Vol.60 (6), p.722-733
Hauptverfasser: Liu, Yuejian, Badée, Justine, Takahashi, Ryan H., Schmidt, Stephan, Parrott, Neil, Fowler, Stephen, Mackenzie, Peter I., Coughtrie, Michael W. H., Collier, Abby C.
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Sprache:eng
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Zusammenfassung:Uridine diphosphate glucuronosyltransferases (UGTs) catalyze glucuronidation to facilitate systemic and local clearance of numerous chemicals and drugs. To investigate whether UGT expression is coregulated in human liver, we analyzed the protein expression of UGTs 1A1, 1A3, 1A4, 1A6, 1A9, 2B7, 3A1, and 3A2 using western blots from 164 healthy human liver samples, comparing expression with age and sex. UGT1A6 levels were significantly higher in children than adults, and UGT3A1 and 3A2 expression significantly increased with age from childhood to age >65 yearas. In children aged 18 years. UGT1A3 expression was always significantly correlated with other UGT1A isoforms in all adults aged >18 years. In individuals aged ≥12 years, expression of UGT1A1/1A4, UGT1A1/1A6, UGT1A1/1A9, and UGT1A4/1A6 significantly correlated, which was not observed in children aged
ISSN:0091-2700
1552-4604
DOI:10.1002/jcph.1571