Expression and Functional Activity of Breast Cancer Resistance Protein (Bcrp, Abcg2) Transporter in the Human Choriocarcinoma Cell Line Bewo

Čečková, Martina; Libra, Antonín; Pávek, Petr; Nachtigal, Petr; Brabec, Marianne; Fuchs, Renate; Štaud, František

doi:10.1111/j.1440-1681.2006.04324.x

Cited by 75 publications

(56 citation statements)

References 40 publications

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“…This protein is able to export a broad range of substrates, which have been reported to include bile acids [7] . BCRP has been detected in the apical membrane of trophoblasts and in fetal vessels [64,74] . Both the mRNA and protein levels of Bcrp are higher in rodent placenta during mid-gestation but decrease at term [75] .…”

Section: Excretion Of Bile Acidsmentioning

confidence: 99%

Excretion of biliary compounds during intrauterine life

Macı́as¹,

Marin²,

Serrano³

2009

WJG

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In adults, the hepatobiliary system, together with the kidney, constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine, respectively. However, during intrauterine life the biliary route of excretion for cholephilic compounds, such as bile acids and biliary pigments, is very poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem.

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Section: Excretion Of Bile Acidsmentioning

confidence: 99%

Excretion of biliary compounds during intrauterine life

Macı́as¹,

Marin²,

Serrano³

2009

WJG

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“…Real-time PCR was performed as described previously. 22,23) Briefly, total RNA was isolated from arteries using Tripure reagent (Roche Diagnostics, Mannheim, Germany) according to the manufacturer's instructions. The RNA samples were dissolved in nucleasefree water and treated with 5 U of DNase I (Takara, Shiga, Japan) for 30 min at 37°C.…”

Section: Rna Preparation and Real-time Polymerase Chain Reaction (Pcr)mentioning

confidence: 99%

Panax notoginseng Saponins Attenuate Atherogenesis Accelerated by Zymosan in Rabbits

Liu

Zhang

Jia

et al. 2010

Biological & Pharmaceutical Bulletin

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Panax notoginseng saponins (PNS) are highly valued traditional Chinese medicine. The effects of PNS (120 mg/kg, once daily administrated intragastrically (i.g.)) on atherosclerosis induced by a high-cholesterol diet and chronic inflammation, which was derived through zymosan (10 mg/kg, once every 2 d) administration intraperitoneally, were evaluated in rabbits for 8 weeks. A normal group, a simple high-fat diet group, and a zymosan plus high-cholesterol diet group (Zym) were used as controls. Typical pathologic changes associated with atherosclerosis in rabbits following induction by zymosan were alleviated by PNS treatment. After 2, 4, 6, and 8 weeks of treatment, PNS decreased the serum levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, interleukin-6 and C-reactive protein as well as increased high-density lipoprotein cholesterol level significantly in comparison with those in the Zym group, except for triglycerides at week 2. In addition, PNS treatment significantly decreased the mRNA expression levels of monocyte chemoattactant protein-1 and nuclear factor-kB/p65 in the aorta wall after 8 weeks of treatment compared with the Zym group. In conclusion, PNS attenuates atherogenesis through an antiinflammatory action and regulation of the blood lipid profile.

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“…These proteins play prominent roles in effluxing drugs and toxic metabolites out of the fetoplacental compartment (Lankas et al, 1998;Jonker et al, 2000). Interestingly, BCRP is also expressed in endothelial cells lining the fetal capillaries (Ceckova et al, 2006), suggesting that it may also serve to pump substrates out of the placenta and into the fetal circulation. The two predominantly basolateral (i.e., fetal-facing) ABC transporters, MDR3/ABCB4 and multidrug resistance protein 1 (MRP1/ABCC1), transport their substrates from mother to fetus, vectorially opposite to MDR1 and BCRP.…”

mentioning

confidence: 99%

Independent Regulation of Apical and Basolateral Drug Transporter Expression and Function in Placental Trophoblasts by Cytokines, Steroids, and Growth Factors

Evseenko

Paxton²,

Keelan³

2007

Drug Metabolism and Disposition

166

135

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ABSTRACT:Placental ATP binding cassette (ABC) transporters protect placental and fetal tissues by effluxing xenobiotics and endogenous metabolites. We have investigated the effects of cytokines and survival/growth factors, implicated in various placental pathologies, on ABC transporter expression and function in primary placental trophoblast cells. Treatment of primary term trophoblasts in vitro with tumor necrosis factor-␣ (TNF-␣) or interleukin (IL)-1␤ decreased mRNA and protein expression of apical transporters ABCB1/multidrug resistance gene product 1 (MDR1) and ABCG2/ breast cancer resistance protein (BCRP) protein by 40 to 50% (P < 0.05). In contrast, IL-6 increased mRNA and protein expression of the basolateral transporter ABCB4/MDR3 (P < 0.05), whereas ABCC1/MRP1 expression was unaltered. Pretreatment of trophoblasts with TNF-␣ over 48 h resulted in significantly decreased BCRP efflux activity (increased mitoxantrone accumulation) with minimal changes in MDR1/3 activity. Epidermal growth factor (EGF) and insulin-like growth factor II, on the other hand, significantly increased BCRP expression at the mRNA and protein level (P < 0.05); EGF treatment also increased BCRP functional activity. Estradiol stimulated BCRP, MDR1, and MDR3 mRNA and protein expression by 40 to 60% and increased MDR1/3 functional activity (P < 0.05). Progesterone had modest positive effects on MRP1 mRNA and MDR1 protein expression (P < 0.05). In conclusion, this study shows that proinflammatory cytokines, sex steroids, and growth factors exert independent effects on expression of apical and basolateral placental ABC transporters in primary trophoblast. Such changes could alter placental drug disposition, increase fetal susceptibility to toxic xenobiotics, and impact on placental viability and function.

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Expression and Functional Activity of Breast Cancer Resistance Protein (Bcrp, Abcg2) Transporter in the Human Choriocarcinoma Cell Line Bewo

Cited by 75 publications

References 40 publications

Excretion of biliary compounds during intrauterine life

Excretion of biliary compounds during intrauterine life

Panax notoginseng Saponins Attenuate Atherogenesis Accelerated by Zymosan in Rabbits

Independent Regulation of Apical and Basolateral Drug Transporter Expression and Function in Placental Trophoblasts by Cytokines, Steroids, and Growth Factors

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