Proteomics of human liver membrane transporters: a focus on fetuses and newborn infants.
Eur J Pharm Sci
; 124: 217-227, 2018 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-30171984
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
We analyzed 36 fetal (median GA 23.4â¯weeks [range 15.3-41.3]), 12 premature newborn (GA 30.2â¯weeks [24.9-36.7], PNA 1.0â¯weeks [0.14-11.4]), 10 term newborn (GA 40.0â¯weeks [39.7-41.3], PNA 3.9â¯weeks [0.3-18.1]), 4 pediatric (PNA 4.1â¯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 postmenstrual age. For most transporters mRNA and protein expression were not correlated. No genotype-protein expression relationship was detected. DISCUSSION ANDCONCLUSION:
Various developmental patterns of protein expression of hepatic transporters emerged in fetuses and newborns up to four months of age. Postmenstrual age was the most robust factor predicting transporter expression in this cohort. Our data fill an important gap in current pediatric transporter ontogeny knowledge.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
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Feto
/
Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Animals
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Child
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Child, preschool
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Humans
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Infant
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Newborn
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article