Effects of maturation on RNA transcription and protein expression of four MRP genes in human placenta and in BeWo cells

Pascolo, Lorella; Fernetti, Cristina; Pirulli, Doroti; Crovella, Sérgio; Amoroso, Antonio; Tiribelli, Claudio

doi:10.1016/s0006-291x(03)00327-9

Cited by 87 publications

(67 citation statements)

References 28 publications

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“…In contrast, the low-level expression of MRP1 found in the basolateral membrane of syncytiotrophoblasts rather serves as a defense system for the trophoblast itself or possibly mediates the transport of important metabolites across the maternal-fetal interface [83,104]. In accordance with this notion, an increase in MRP1 expression can be observed with placental maturation [120,147]. In the testis, MRP1 most probably plays a role in the local defense, protecting the special cell types such as the Sertoli cells and the developing spermatocytes in the seminiferous tubules.…”

Section: Dual Role Of Mrp1 In the Physiological Barriersmentioning

confidence: 83%

Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1)

Bakos

Homolya

2006

Pflugers Arch - Eur J Physiol

153

104

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MRP1 (ABCC1) is a peculiar member of the ABC transporter superfamily for several aspects. This protein has an unusually broad substrate specificity and is capable of transporting not only a wide variety of neutral hydrophobic compounds, like the MDR1/P-glycoprotein, but also facilitating the extrusion of numerous glutathione, glucuronate, and sulfate conjugates. The transport mechanism of MRP1 is also complex; a composite substratebinding site permits both cooperativity and competition between various substrates. This versatility and the ubiquitous tissue distribution make this transporter suitable for contributing to various physiological functions, including defense against xenobiotics and endogenous toxic metabolites, leukotriene-mediated inflammatory responses, as well as protection from the toxic effect of oxidative stress. In this paper, we give an overview of the considerable amount of knowledge which has accumulated since the discovery of MRP1 in 1992. We place special emphasis on the structural features essential for function, our recent understanding of the transport mechanism, and the numerous assignments of this transporter.

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Section: Dual Role Of Mrp1 In the Physiological Barriersmentioning

confidence: 83%

Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1)

Bakos

Homolya

2006

Pflugers Arch - Eur J Physiol

153

104

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“…ABCB1 is highly expressed in human placenta during early gestation, [17][18][19] while ABCG2 is expressed more in mid gestation. 20 During late gestation, ABCC1 21 and ABCC2 22 show the highest placental expression. Therefore, we can speculate that ABCB1 is vital in protecting the early fetus from xenobiotics insult, 23,24 such as maternal pharmacotherapy and even fetal waste products, while ABCC1, ABCC2, and ABCG2 can provide better protection to the mature fetus.…”

Section: Discussionmentioning

confidence: 99%

Fetal polymorphisms at the ABCB1-transporter gene locus are associated with susceptibility to non-syndromic oral cleft malformations

et al. 2013

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ATP-binding cassette (ABC) proteins in the placenta regulate fetal exposure to xenobiotics. We hypothesized that functional polymorphisms in ABC genes influence risk for non-syndromic oral clefts (NSOC). Both family-based and case-control studies were undertaken to evaluate the association of nine potentially functional single-nucleotide polymorphisms within four ABC genes with risk of NSOC. Peripheral blood DNA from a total of 150 NSOC case-parent trios from Singapore and Taiwan were genotyped, as was cord blood DNA from 189 normal Chinese neonates used as controls. In trios, significant association was observed between the ABCB1 single-nucleotide polymorphisms and NSOC (Po0.05). Only ABCB1 rs1128503 retained significant association after Bonferroni correction (odds ratio (OR) ¼ 2.04; 95% confidence interval (CI) ¼ 1.42-2.98), while rs2032582 and rs1045642 showed nominal significance. Association with rs1128503 was replicated in a case-control analysis comparing NSOC probands with controls (OR ¼ 1.58; 95% CI ¼ 1.12-2.23). A comparison between the mothers of probands and controls showed no evidence of association, suggesting NSOC risk is determined by fetal and not maternal ABCB1 genotype. The two studies produced a combined OR of 1.79 (95% CI ¼ 1.38-2.30). The T-allele at rs1128503 was associated with higher risk. This study thus provides evidence that potentially functional polymorphisms in fetal ABCB1 modulate risk for NSOC, presumably through suboptimal exclusion of xenobiotics at the fetal-maternal interface.

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“…It is primarily speculated that MRPs appear to efflux polar compounds and conjugated metabolites in particular unconjugated bilirubin and bile acids (Borst et al, 2000;Bodó et al, 2003). Although there are some controversies about the cellular localization of different MRPs in human placenta, most of the MRPs (MRP1-6, and MRP7) have been found in human placenta (Langmann et al, 2003;Litman et al, 2001;Keppler et al, 1998;Bera et al, 2001;Ozvegy et al, 2001;Sato et al, 2003;Pascolo et al, 2003). MRPs proteins are associated with the removal of glutathione (GSH), glucuronide or sulphate conjugated metabolites from cells (Mathias et al, 2005;St-Pierre et al, 2002).…”

Section: Multi-drug-resistance Associated Proteins (Mrps)mentioning

confidence: 99%

“…It has also been reported that some unmodified toxins and drugs are transported by the MRP family (Keppler et al, 1998;Nagashige et al, 2003). The specific roles of MRPs in placenta have not been defined, but they perform efflux of polar conjugates xenobiotics or metabolites of endogenous compounds (Pascolo et al, 2003;Leazer & Klaassen, 2003).…”

Section: Multi-drug-resistance Associated Proteins (Mrps)mentioning

confidence: 99%

ABC Transporters in Human Placenta and Their Role in Maternal-Fetal Cholesterol Transfer: ABCA1 Candidate Target

Bhattacharjee¹,

Ietta²,

Romagnoli³

et al. 2012

Recent Advances in Research on the Human Placenta

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Effects of maturation on RNA transcription and protein expression of four MRP genes in human placenta and in BeWo cells

Cited by 87 publications

References 28 publications

Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1)

Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1)

Fetal polymorphisms at the ABCB1-transporter gene locus are associated with susceptibility to non-syndromic oral cleft malformations

ABC Transporters in Human Placenta and Their Role in Maternal-Fetal Cholesterol Transfer: ABCA1 Candidate Target

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