Proteomics of human liver membrane transporters: a focus on fetuses and newborn infants

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Bianca D van GroenSaskia N de Wildt

Abstract

Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples. Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3, NTCP, OCT1, OATP1B1, OATP1B3, OATP2B1 and ATP1A1 were quantified with LC-MS/MS in isolated crude membrane fractions of snap-frozen post-mortem fetal and pediatric, and surgical adult liver samples. mRNA expression was quantified using RNA sequencing, and genetic variants with TaqMan assays. We explored relationships between protein expression and age (gestational age [GA], postnatal age [PNA], and postmenstrual age); between protein and mRNA expression; and between protein expression and genotype. We analyzed 36 fetal (median GA 23.4 weeks [range 15.3-41.3]), 12 premature newborn (GA 30.2 weeks [24.9-36.7], PNA 1.0 weeks [0.14-11.4]), 10 term newborn (GA 40.0 weeks [39.7-41.3], PNA 3.9 weeks [0.3-18.1]), 4 pediatric (PNA 4.1 years [1.1-7.4]) and 8 adult liver samples. A relationship with age was found for BCRP, BSEP, GLUT1, MDR1, MRP1, MRP2, MRP3, NTCP, OATP1B1 and OCT1, with the strongest relationship for...Continue Reading

Citations

Dec 18, 2018·Expert Opinion on Drug Metabolism & Toxicology·Anne SmitsKarel Allegaert
Jan 10, 2020·Clinical and Translational Science·Bianca D van GroenJ Steven Leeder
Jul 24, 2020·Clinical and Translational Science·Bianca D van GroenLoeckie de Zwart
Mar 8, 2020·Pharmacological Reviews·Melanie A FelmleeMarilyn E Morris
May 10, 2020·Clinical Pharmacology and Therapeutics·Bianca D van GroenSaskia N de Wildt
Jun 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jiapeng Li, Hao-Jie Zhu
Feb 29, 2020·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Cordula StillhartAnette Müllertz
Feb 9, 2021·Clinical Chemistry and Laboratory Medicine : CCLM·Mercy ThomasAnushi E Rajapaksa
Apr 2, 2021·Biochemical Pharmacology·Jonny KinziHenriette E Meyer Zu Schwabedissen
Sep 23, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Márton KissSaskia N de Wildt

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