Protein Abundance of Clinically Relevant Drug Transporters in The Human Kidneys.
ATP Binding Cassette Transporter, Subfamily G, Member 2
/ genetics
Adult
Age Factors
Aged
Chromatography, High Pressure Liquid
Female
Humans
Kidney Cortex
/ metabolism
Male
Middle Aged
Organic Anion Transport Protein 1
/ genetics
Organic Cation Transport Proteins
/ genetics
Organic Cation Transporter 2
/ genetics
Proteome
/ analysis
Sex Factors
Tandem Mass Spectrometry
age
gender
human kidneys
protein expression
transporters
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
24 Oct 2019
24 Oct 2019
Historique:
received:
29
09
2019
revised:
21
10
2019
accepted:
22
10
2019
entrez:
27
10
2019
pubmed:
28
10
2019
medline:
7
3
2020
Statut:
epublish
Résumé
Renal drug transporters such as the organic cation transporters (OCTs), organic anion transporters (OATs) and multidrug resistance proteins (MRPs) play an important role in the tubular secretion of many drugs influencing their efficacy and safety. However, only little is known about the distinct protein abundance of these transporters in human kidneys, and about the impact of age and gender as potential factors of inter-subject variability in their expression and function. The aim of this study was to determine the protein abundance of MDR1, MRP1-4, BCRP, OAT1-3, OCT2-3, MATE1, PEPT1/2, and ORCTL2 by liquid chromatography-tandem mass spectrometry-based targeted proteomics in a set of 36 human cortex kidney samples (20 males, 16 females; median age 53 and 55 years, respectively). OAT1 and 3, OCT2 and ORCTL2 were found to be most abundant renal SLC transporters while MDR1, MRP1 and MRP4 were the dominating ABC transporters. Only the expression levels of MDR1 and ORCTL2 were significantly higher abundant in older donors. Moreover, we found several significant correlations between different transporters, which may indicate their functional interplay in renal vectorial transport processes. Our data may contribute to a better understanding of the molecular processes determining renal excretion of drugs.
Identifiants
pubmed: 31653114
pii: ijms20215303
doi: 10.3390/ijms20215303
pmc: PMC6862022
pii:
doi:
Substances chimiques
ATP Binding Cassette Transporter, Subfamily G, Member 2
0
Organic Anion Transport Protein 1
0
Organic Cation Transport Proteins
0
Organic Cation Transporter 2
0
Proteome
0
SLC22A18 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 107/11-1
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