Expression of ABC Efflux Transporters in Placenta from Women with Insulin-Managed Diabetes

Anger, G; Cressman, Alex; Piquette-Miller, Micheline

doi:10.1371/journal.pone.0035027

Cited by 41 publications

(23 citation statements)

References 50 publications

(58 reference statements)

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“…Methods for RNA isolation, cDNA synthesis, and quantitative polymerase chain reaction (qPCR) have been described previously (Anger et al, 2012). Briefly, RNA was extracted from ;75 mg of snap-frozen tissue using TriZol reagent (Invitrogen, Carlsbad, CA) and cDNA was synthesized from 2 mg of DNAse I treated RNA using the High-Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Burlington, ON, Canada) according to manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…qPCR oligonucleotides were synthesized at The Hospital for Sick Children (DNA Synthesis Centre, Toronto, ON, Canada) and reconstituted in nuclease-free DEPC H 2 O (Table 1). Amplicon sequences were amplified as described elsewhere (Anger et al, 2012). Melt-curve analysis was used to ensure primer specificity.…”

Section: Methodsmentioning

confidence: 99%

“…Given the dissimilar changes seen in the expression of the Abcb1a and Abcb1b mRNA in several tissues and the fact that both of these mRNA encode for the MDR1 protein in mice, we further investigated the impact of malaria on the protein expression of MDR1. Methods for protein isolation and Western blotting have been described previously (Anger et al, 2012). Briefly, protein samples were isolated from 300 mg of snap-frozen tissue homogenized in lysis buffer containing dithiothrietol (1 mM; Sigma-Aldrich), phenylmethylsulfonyl fluoride (0.5 mM; BioShop Canada Inc., Burlington, ON, Canada), and 1Â protease-inhibitor cocktail (Sigma-Aldrich) at 4°C.…”

Section: Methodsmentioning

confidence: 99%

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Malaria Infection Alters the Expression of Hepatobiliary and Placental Drug Transporters in Pregnant Mice

et al. 2013

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Preventing and treating malaria in pregnancy is a global health priority. However little is known regarding the impact of malaria infection on the maternal and fetal disposition of pharmaceuticals and other xenobiotics. Our objective was to characterize expression of key determinants of drug-disposition in maternal and fetal tissues in a validated murine model of experimental placental malaria. Balb/c mice were infected with Plasmodium berghei at mid gestation [gestational day (GD) 13] and maternal, placental, and fetal tissues were collected at GD19. Expression of key ABC drug transporters and Cyp3a11 was examined by quantitative polymerase chain reaction. Western blotting was used to examine the protein expression of multidrug resistance protein 1 (MDR1, ABCB1). Compared with controls, placental mRNA expression of Abcb1a, Abcb1b, Abcc1, Abcc2, Abcc3, and Abcg2 were significantly downregulated in the malaria-infected group (P < 0.05), as was placental MDR1 protein (P < 0.05). Significantly decreased hepatic expression of Abcc2, Abcg2, and Abcb11 and significantly increased expression of Abcb1b, Abcc1, and Abcc3 were seen in malaria-infected dams (P < 0.05) in comparison with uninfected controls. The expression of Abcb1a and Abcg2 was significantly decreased in fetal liver of infected dams, whereas levels of Abcb1b were increased (P < 0.05). Maternal and fetal hepatic expression of Cyp3a11 was significantly downregulated in the malaria group (P < 0.05). Together, malaria-induced alterations in the expression of transporters and drug-metabolizing enzymes in maternal and fetal tissues may alter the disposition of endogenous and therapeutic substrates, potentially impacting maternal and fetal outcomes.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Malaria Infection Alters the Expression of Hepatobiliary and Placental Drug Transporters in Pregnant Mice

et al. 2013

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“…Protein extraction was performed by methods as described previously (29,30) . Briefly, 300 mg of liver tissue were band was determined with the AlphaEaseFC software (Alpha Innotech).…”

Section: Western Blot Analysismentioning

confidence: 99%

Effect of a high-fat diet on the hepatic expression of nuclear receptors and their target genes: relevance to drug disposition

et al. 2015

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More than 1·4 billion individuals are overweight or obese worldwide. While complications often require therapeutic intervention, data regarding the impact of obesity on drug disposition are scarce. As the influence of diet-induced obesity on drug transport and metabolic pathways is currently unclear, the objective of the present study was to investigate the effect of high fat feeding for 13 weeks in female Sprague -Dawley rats on the hepatic expression of the nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), liver X receptor (LXR) and farnesoid X receptor (FXR) and several of their target genes. We hypothesised that high fat feeding would alter the gene expression of major hepatic transporters through a dysregulation of the expression of the nuclear receptors. The results demonstrated that, along with a significant increase in body fat and weight, a high-fat diet (HFD) induced a significant 2-fold increase in the expression of PXR as well as a 2-, 5-and 2·5-fold increase in the hepatic expression of the PXR target genes Abcc2, Abcb1a and Cyp3a2, respectively (P,0·05). The expression levels of FXR were significantly increased in rats fed a HFD in addition to the increase in the expression levels of FXR target genes Abcb11 and Abcb4. The expression levels of both LXRa and LXRb were slightly but significantly increased in rats fed a HFD, and the expression levels of their target genes Abca1 and Abcg5, but not Abcg8, were significantly increased. The expression of the nuclear receptor CAR was not significantly altered between the groups. This suggests that a HFD may induce changes in the hepatobiliary transport and metabolism of endogenous and exogenous compounds.

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“…It also implies that the transport of drugs by ABC transporters across the placenta could be affected and that certain GDM treatments based on these transporters could be less efficient than expected [50]. Anger et al [51] have shown that the placental protein expression of other ABC transporters (MDR1, MRP2, BCRP) is not altered in GDM pregnancies. However, this study has not taken into account the maternal BMI.…”

Section: Dubé Et Almentioning

confidence: 99%

Modulation of Cholesterol Transport by Insulin-Treated Gestational Diabetes Mellitus in Human Full-Term Placenta1

Dubé

Éthier-Chiasson

Lafond

2013

Biology of Reproduction

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Gestational diabetes mellitus (GDM) is a common complication of pregnancy that is characterized by glucose intolerance, leads to dyslipidemia, and is aggravated by obesity. Cholesterol is taken up by the placenta as part of lipoproteins through the scavenger receptor class B type I receptor (SRBI), low-density lipoprotein receptor (LDLR), and very low density lipoprotein receptor (VLDLR), and its efflux is then mediated by ABCA1 and ABCG1. PCSK9 is involved in the degradation of LDLR and VLDLR. The goal of this study was to evaluate the impact of GDM and prepregnancy body mass index (BMI) on cholesterol transport through the modulation of the expression of several key players. Human full-term placenta, maternal, and venous cord blood samples were obtained at delivery from normal-weight women without GDM (n = 10), normal-weight women with GDM (n = 6), and overweight/obese women with GDM (n = 6). Lipids (total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, free fatty acids, apolipoprotein A1, apolipoprotein B100) levels were evaluated in blood samples. Messenger RNA and protein expression levels (LDLR, VLDLR, SRBI, ABCA1, ABCG1, proprotein convertase subtilisin/kexin type 9, liver x receptors, peroxisome proliferator-activated receptors) were assessed in human full-term placenta, respectively, by real-time RT-PCR and Western blots. Lipoprotein lipase activity was evaluated using a commercial kit on tissue homogenates. Overall, our study demonstrates that GDM affects the maternal and neonatal lipid profiles as well as different key players of placental cholesterol transfer from the maternal to the fetal circulation, depending on the maternal BMI. These changes could affect the fetal metabolism and predispose the fetus to future metabolic diseases.

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Expression of ABC Efflux Transporters in Placenta from Women with Insulin-Managed Diabetes

Cited by 41 publications

References 50 publications

Malaria Infection Alters the Expression of Hepatobiliary and Placental Drug Transporters in Pregnant Mice

Malaria Infection Alters the Expression of Hepatobiliary and Placental Drug Transporters in Pregnant Mice

Effect of a high-fat diet on the hepatic expression of nuclear receptors and their target genes: relevance to drug disposition

Modulation of Cholesterol Transport by Insulin-Treated Gestational Diabetes Mellitus in Human Full-Term Placenta1

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