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The human Multidrug Resistance-associated Protein MRP1 mediates ATP-dependent transport of unconjugated bilirubin
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IN VIVO AND IN VITRO HEPATIC TRANSPORT OF THE MAGNETIC RESONANCE IMAGING CONTRAST AGENT B ROLE OF MRPS.
No full textEffects of maturation on RNA transcription and protein expression of 4 MRP genes in human placenta and in BeWo cells.
No full textThe placenta is a multifunctional organ that protects the fetus from toxic compounds and the MRPs contribute to this function. The expression of MRP1, MRP2, MRP3, and MRP5 was compared in human placental tissue and in BeWo cells by real-time RT-PCR analysis; protein expression was assessed by Western blot. MRP1 and MRP3 were the most abundantly expressed genes in placenta but only MRP1 was highly expressed in the BeWo cells. Expression of MRP1 increased 4-fold in the third as compared with first trimester placental samples, and increased 20-fold with polarization of BeWo cells. MRP2, MRP3, and MRP5 were weakly expressed both in placenta and BeWo cells. Protein expression followed mRNA quantification for MRP1 and MRP5 but not for MRP2 and MRP3. These data indicated that MRP1 and MRP5 increase with trophoblast maturation, suggesting a particular role for these proteins in the organ functional development
MRP 1 at apical (maternal-facing) pole of human trophoblasts accounts for the placental transfer of unconjugated bilirubin (UCB) from the fetal to the maternal circulation
No full textMolecular determinants in the transport of a bile acid derived diagnostic agent in tumoral and non-tumoral cell lines of human liver.
No full textContrast-enhanced magnetic resonance imaging (CE-MRI) is a valuable technique for the diagnosis of liver diseases. As gadocoletic acid trisodium salt (B22956/1), a new contrast agent showing high biliary excretion, may be potentially advantageous in hepatobiliary imaging, the aim of the study was to investigate the molecular mechanisms of hepatic transport of the B22956 ion in a cellular model of hepatic tumor. B22956 ion uptake was measured in tumoral (HepG2) and nontumoral (Chang liver) hepatic cell lines. Absolute quantitative real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) analyses, using cloned PCR products as standards, were performed on total RNA of both cell lines and normal liver to evaluate the transcription of 12 transport genes: SLCO1A2, SLCO2B1, SLCO1B1, SLCO3A1, SLCO4A1, SLCO1B3, SLC22A7, SLC22A8, SLC22A1, SLC10A1, SLC15A1, and SLC15A2. B22956 transport was more efficient in Chang liver than in HepG2 cells and was inhibited by cholecystokinin-8, a specific substrate of OATP1B3. Real-time RT-PCR analyses revealed different transcription profiles in the tumoral and nontumoral cell lines. Compared with normal liver, the expression of SLCO1B1, SLCO3A1, and SLCO1B3 was greatly repressed in HepG2 cells, whereas SLCO2B1, SLC22A7, and SLC22A8 expression was either maintained or increased. On the contrary, in Chang liver cells, SLC22A7 and SLC22A8 genes were undetectable, whereas the expression of SLCO3A1, SLCO4A1, and SLCO1B3 was similar to normal liver. Transport studies and gene expression analyses indicated that B22956 ion is a good substrate to the liver-specific OATP1B3, reported to be poorly expressed or absent in human liver tumors. Therefore, B22956 may be helpful in detecting hepatic neoplastic lesions by CE-MRI
MECHANISMS FOR THE TRANSPORT OF UNCONJUGATED BILIRUBIN IN HUMAN TROPHOBLASTIC BEWO CELLS
No full textMagnetic Resonance Contrast Agents: From the Bench to the Patient.
No full textMagnetic Resonance Imaging is gaining a prominent role in the routine clinical investigation. To further improve this technique it is crucial that contrast agents are developed with more optimal organ specificity. This will not only result in a better diagnostic efficiency but also in a reduction of the amount of the agent administered. A combination of techniques has been employed to increase the target selectivity of the contrast agent and thereby the feasibility to visualize different organs. The organ targeting is based on the understanding of the mechanisms involved in the interaction of the agent with plasma proteins (albumin in particular) as well as the different membrane transporters involved in the uptake and in the excretion of the agent from the organ. The physicochemical properties of the contrast agents play a major role in the interaction with these various proteins. In this review we address the relationship between the structure of the contrast agents and their binding to different plasma proteins and membrane transporters in different organs, with special reference to the liver and kidney. The present and potentially future applications of these concepts in the clinical setting are also discussed
Effects of maturation on RNA transcription and protein expression of four MRP genes in human placenta and in BeWo cells
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