A Comprehensive Analysis of Ontogeny of Renal Drug Transporters: mRNA Analyses, Quantitative Proteomics, and Localization

Autor: Kit Wun Kathy Cheung, Marjolein van Borselen, Y. Simons-Oosterhuis, Bianca D van Groen, Kathleen M. Giacomini, Dick Tibboel, Saskia N. de Wildt, Edwin Spaans, Bart Smeets, Lei Zhang, Adrianus C. J. M. de Bruijn, Robert M. Verdijk, Shiew-Mei Huang, Janneke N. Samsom
Přispěvatelé: Pediatric Surgery, Gastroenterology & Hepatology, Pediatrics, Pathology, Clinical Genetics
Rok vydání: 2019
Předmět:
Proteomics
Male
Kidney Disease
Organic anion transporter 1
Abcg2
Messenger
030226 pharmacology & pharmacy
0302 clinical medicine
Tandem Mass Spectrometry
Pharmacology (medical)
Pharmacology & Pharmacy
Child
Cancer
Chromatography
Liquid
Kidney
Pregnane X receptor
biology
Chemistry
Age Factors
Pregnane X Receptor
Articles
Pharmacology and Pharmaceutical Sciences
Middle Aged
3. Good health
Real-time polymerase chain reaction
medicine.anatomical_structure
Biochemistry
5.1 Pharmaceuticals
Generic Health Relevance
Child
Preschool
030220 oncology & carcinogenesis
Female
Adult
Kidney Cortex
Adolescent
1.1 Normal biological development and functioning
Quantitative proteomics
Real-Time Polymerase Chain Reaction
Article
Young Adult
03 medical and health sciences
medicine
Humans
RNA
Messenger
Preschool
Aged
Pharmacology
Messenger RNA
Research
Prevention
Infant
Newborn
Membrane Transport Proteins
Infant
Transporter
Newborn
Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]
biology.protein
RNA
Antimicrobial Resistance
Renal disorders Radboud Institute for Health Sciences [Radboudumc 11]
Chromatography
Liquid
Zdroj: Clinical Pharmacology and Therapeutics, 106, 1083-1092
Clinical Pharmacology & Therapeutics, 106(5), 1083-1092. Wiley-Blackwell
Clinical Pharmacology and Therapeutics, 106, 5, pp. 1083-1092
Clinical pharmacology and therapeutics, vol 106, iss 5
Clinical Pharmacology and Therapeutics
ISSN: 0009-9236
Popis: Contains fulltext : 209000.pdf (Publisher’s version ) (Open Access) Human renal membrane transporters play key roles in the disposition of renally cleared drugs and endogenous substrates, but their ontogeny is largely unknown. Using 184 human postmortem frozen renal cortical tissues (preterm newborns to adults) and a subset of 62 tissue samples, we measured the mRNA levels of 11 renal transporters and the transcription factor pregnane X receptor (PXR) with quantitative real-time polymerase chain reaction, and protein abundance of nine transporters using liquid chromatography tandem mass spectrometry selective reaction monitoring, respectively. Expression levels of p-glycoprotein, urate transporter 1, organic anion transporter 1, organic anion transporter 3, and organic cation transporter 2 increased with age. Protein levels of multidrug and toxin extrusion transporter 2-K and breast cancer resistance protein showed no difference from newborns to adults, despite age-related changes in mRNA expression. Multidrug and toxin extrusion transporter 1, glucose transporter 2, multidrug resistance-associated protein 2, multidrug resistance-associated protein 4 (MRP4), and PXR expression levels were stable. Using immunohistochemistry, we found that MRP4 localization in pediatric samples was similar to that in adult samples. Collectively, our study revealed that renal drug transporters exhibited different rates and patterns of maturation, suggesting that renal handling of substrates may change with age.
Databáze: OpenAIRE
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