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Tissue distribution and ontogeny of multidrug resistance protein 2, a phosphatidylcholine translocator, in rats

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Abstract

Multidrug resistance protein 2 (Mdr2), encoded by ATP-binding cassette b4 (Abcb4), serves as a phospholipid flippase that is indispensable for phosphatidylcholine translocation. However, little was known about the regulation of Mdr2 in Sprague–Dawley rats, although they are commonly used for pre-clinical investigation as well as mechanistic study. Present study aims at determining the tissue distribution, gender difference and ontogeny of Mdr2 in rats on both gene and protein levels. Results showed that Mdr2 was highly expressed in liver, modestly enriched in brain and testis, and less distributed in gastrointestinal tracts. Gender-divergent and male-dominated distribution was observed in the Mdr2 mRNA expression of liver and generative organs. Developmental pattern of rat Mdr2 on protein level was not exactly consistent with that on mRNA level. In conclusion, there was a considerable distribution of rat Mdr2 in the brain, testis and intestine besides liver, and the ontogeny of Mdr2 performed in an age-dependent pattern with the post-transcriptional regulation.

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Abbreviations

MDR/Mdr:

Multidrug resistance protein

Abcb4:

ATP-binding cassette b4

PC:

Phosphatidylcholine

PCR:

Polymerase chain reaction

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GE:

Gene expression values

Ct:

Comparative threshold cycle

References

  • Chen HL, Chen HL, Liu YJ, Feng CH, Wu CY, Shyu MK, Yuan RH, Chang MH (2005) Developmental expression of canalicular transporter genes in human liver. J Hepatol 43:472–477

    Article  PubMed  CAS  Google Scholar 

  • Cui YJ, Cheng X, Weaver YM, Klaassen CD (2009) Tissue distribution, gender-divergent expression, ontogeny, and chemical induction of multidrug resistance transporter genes (Mdr1a, Mdr1b, Mdr2) in mice. Drug Metab Dispos 37:203–210

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Honda A, Ikegami T, Nakamuta M, Miyazaki T, Iwamoto J, Hirayama T, Saito Y, Takikawa H, Imawari M, Matsuzaki Y (2013) Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. Hepatology 57:1931–1941

    Article  PubMed  CAS  Google Scholar 

  • Langmann T, Mauerer R, Schmitz G (2006) Human atp-binding cassette transporter taqman low-density array: analysis of macrophage differentiation and foam cell formation. Clin Chem 52:310–313

    Article  PubMed  CAS  Google Scholar 

  • Mauad TH, van Nieuwkerk CM, Dingemans KP, Smit JJ, Schinkel AH, Notenboom RG, van den Bergh Weerman MA, Verkruisen RP, Groen AK, Oude Elferink RP, van der Valk MA, Borst P, and Offerhaus GJ (1994) Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis. Am J Pathol 145:1237–1245

  • Ostlund G, Sonnhammer EL (2012) Quality criteria for finding genes with high mRNA–protein expression correlation and coexpression correlation. Gene 497:228–236

    Article  PubMed  Google Scholar 

  • Oude Elferink RP, Paulusma CC (2007) Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein). Pflugers Arch 453:601–610

    Article  PubMed  CAS  Google Scholar 

  • Smith AJ, van Helvoort A, van Meer G, Szabo K, Welker E, Szakacs G, Varadi A, Sarkadi B, Borst P (2000) MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J Biol Chem 275:23530–23539

    Article  PubMed  CAS  Google Scholar 

  • Spencer ES, Minch J, Lahmers KK, Haldorson GJ, Mealey KL (2010) Canine ABCB4: tissue expression and cDNA structure. Res Vet Sci 89:65–71

    Article  PubMed  CAS  Google Scholar 

  • Taipalensuu J, Törnblom H, Lindberg G, Einarsson C, Sjöqvist F, Melhus H, Garberg P, Sjöström B, Lundgren B, Artursson P (2001) Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers. J Pharmacol Exp Ther 299:164–170

    PubMed  CAS  Google Scholar 

  • Warren MS, Zerangue N, Woodford K, Roberts LM, Tate EH, Feng B, Li C, Feuerstein TJ, Gibbs J, Smith B, de Morais SM, Dower WJ, Koller KJ (2009) Comparative gene expression profiles of ABC transporters in brain microvessel endothelial cells and brain in five species including human. Pharmacol Res 59:404–413

    Article  PubMed  CAS  Google Scholar 

  • Yoshikado T, Takada T, Yamamoto T, Yamaji H, Ito K, Santa T, Yokota H, Yatomi Y, Yoshida H, Goto J, Tsuji S, Suzuki H (2011) Itraconazole-induced cholestasis: involvement of the inhibition of bile canalicular phospholipid translocator MDR3/ABCB4. Mol Pharmacol 79:241–250

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was financially supported by Jiangsu province Nanjing City Innovative Graduate Research Program (No. CXZZ11_0828). We would like to acknowledge to Prof. Yubin Zhang and his lab members for their advice and support.

Conflict of interest

Qiuyang Zhang, Wei Yang, Hanlin Song, Hui Wu, Di Zhao, Yang Lu, Jiake He and Xijing Chen declare that they have no conflict of interest.

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Correspondence to Xijing Chen.

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Zhang, Q., Yang, W., Song, H. et al. Tissue distribution and ontogeny of multidrug resistance protein 2, a phosphatidylcholine translocator, in rats. Eur J Drug Metab Pharmacokinet 41, 87–91 (2016). https://doi.org/10.1007/s13318-014-0226-5

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  • DOI: https://doi.org/10.1007/s13318-014-0226-5

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