The Presence of Xenobiotic Transporters in Rat Placenta

Leazer, Tyra M.; Klaassen, Curtis D.

doi:10.1124/dmd.31.2.153

Cited by 114 publications

(82 citation statements)

References 71 publications

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“…The mRNA of genes examined was quantified using Quantigene bDNA signal amplification kit (Bayer Diagnostics, East Walpole, MA) with modifications (Leazer and Klaassen, 2003). The probes for all the rat genes determined herein except Mrp9 have been reported previously (Leazer and Klaassen, 2003). The probes for rat Mrp9 are shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…The bDNA assay is a high-throughput and quantitative method for mRNA quantification (Canales et al, 2006) that has been used extensively in our laboratory (Leazer and Klaassen, 2003;Maher et al, 2005a;Lu et al, 2006). The mRNA of genes examined was quantified using Quantigene bDNA signal amplification kit (Bayer Diagnostics, East Walpole, MA) with modifications (Leazer and Klaassen, 2003).…”

Section: Methodsmentioning

confidence: 99%

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Gender Differences in mRNA Expression of ATP-Binding Cassette Efflux and Bile Acid Transporters in Kidney, Liver, and Intestine of 5/6 Nephrectomized Rats

Lü¹,

Klaassen²

2007

Drug Metab Dispos

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ABSTRACT:ATP-binding cassette (ABC) transporters including multidrug resistance proteins (Mdr), multidrug resistance-associated proteins (Mrp), and breast cancer resistance protein (Bcrp/Abcg2) play major roles in tissue defense. Abcg5/g8 is essential in cholesterol efflux. The present study was aimed at elucidating alteration in expression of these transporters and bile-acid transporters during chronic kidney disease (CKD) and underlying molecular mechanisms. Seven weeks after 5/6 nephrectomy (Nx), mRNA expression of 16 aforementioned transporters in kidney, liver, jejunum, and large intestine of male and female Nx rats was quantified with the branched DNA signal amplification assay. In Nx males, intestinal expression of all the transporters remained unchanged; hepatic expression of most transporters was not altered, except increases in Mdr1a, Mrp3, and Abcg8. In male remnant kidneys, kidneypredominant transporter Abcg2 decreased and correlated with CKD severity, whereas Mdr1b, Mrp3, and ileal bile-acid transporter increased and correlated with CKD severity. Such changes were largely absent in Nx females. Renal alterations of these transporters correlated with increases of cytokines and/or decreases of nuclear receptors such as estrogen receptor ␣ and glucocorticoid receptor. Renal protein expression of Mrp2 increased, whereas that of Mrp4 remained unchanged in both genders of Nx rats. Treatment of rat proximal tubule NRK-52E cells with interleukin (IL)-1␤ and IL-6 increased Mrp3 mRNA expression. In conclusion, during CKD, renal expression of many ABC transporters was altered at the transcriptional level, whereas hepatic mRNA expression of most ABC transporters remained unchanged. Down-regulation of steroid hormone receptors and increase of inflammatory cytokines may contribute to alteration of transporter gene expression in kidney during CKD.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Gender Differences in mRNA Expression of ATP-Binding Cassette Efflux and Bile Acid Transporters in Kidney, Liver, and Intestine of 5/6 Nephrectomized Rats

Lü¹,

Klaassen²

2007

Drug Metab Dispos

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“…These include MRPs, organic anion-transporting polypeptides (OATPs), OATs, organic cation transporters (OCTs), and zinc transporters (Leazer and Klaassen, 2003). The localization of most of these transporters in the placental membrane has not been determined.…”

Section: Molecular Mimicry and The Transport Of Ch 3 Hg + In Placentamentioning

confidence: 99%

Molecular and ionic mimicry and the transport of toxic metals

Bridges

Zalups

2005

Toxicology and Applied Pharmacology

676

460

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Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport of selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.

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“…The PGP transporters are also essential for protection of mammalian embryos. Mice and rats have high levels of PGP transporters in the placenta (22) and in the embryo (23). Embryos of transgenic mice lacking PGP accumulate 5-fold-higher levels of toxic compounds administered to the mothers than their normal, PGPexpressing counterparts.…”

Section: Protective Strategies Integral To Developmental Programsmentioning

confidence: 99%

Embryo stability and vulnerability in an always changing world

Hamdoun

Epel

2007

Proc. Natl. Acad. Sci. U.S.A.

321

266

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Contrary to the view that embryos and larvae are the most fragile stages of life, development is stable under real-world conditions. Early cleavage embryos are prepared for environmental vagaries by having high levels of cellular defenses already present in the egg before fertilization. Later in development, adaptive responses to the environment either buffer stress or produce alternative developmental phenotypes. These buffers, defenses, and alternative pathways set physiological limits for development under expected conditions; teratology occurs when embryos encounter unexpected environmental changes and when stress exceeds these limits. Of concern is that rapid anthropogenic changes to the environment are beyond the range of these protective mechanisms.

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The Presence of Xenobiotic Transporters in Rat Placenta

Cited by 114 publications

References 71 publications

Gender Differences in mRNA Expression of ATP-Binding Cassette Efflux and Bile Acid Transporters in Kidney, Liver, and Intestine of 5/6 Nephrectomized Rats

Gender Differences in mRNA Expression of ATP-Binding Cassette Efflux and Bile Acid Transporters in Kidney, Liver, and Intestine of 5/6 Nephrectomized Rats

Molecular and ionic mimicry and the transport of toxic metals

Embryo stability and vulnerability in an always changing world

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