Histochemistry and Cell Biology

, Volume 127, Issue 5, pp 503–512

Ethanol consumption alters expression and colocalization of bile salt export pump and multidrug resistance protein 2 in the rat

  • Vadim Zinchuk
  • Olga Zinchuk
  • Kunihiro Akimaru
  • Fumio Moriya
  • Teruhiko Okada
Original Paper

Abstract

Chronic ethanol consumption elicits detrimental changes of liver metabolism. By employing a 12-week-long feeding regimen, we investigated the effects of chronic ethanol consumption on the expression and localization of bile salt export pump (Bsep), a major canalicular exporter of bile salts, and multidrug resistance protein 2 (Mrp2), a canalicular organic anion transporter, in the rat liver. RT-PCR, confocal immunofluorescence microscopy, immunoblotting, and quantitative colocalization analysis were used to examine their gene and protein expression, and changes in the distribution of antigenic sites. Bsep mRNA was upregulated, while Mrp2 mRNA responded by downregulation. In agreement with mRNA, the expression of Bsep protein increased, while the expression of Mrp2 protein responded with a decrease, suggesting that the expression of both of them is transcriptionally regulated. Confocal immunofluorescence microscopy showed disruption of the colocalization of Bsep and Mrp2 proteins at the hepatocyte canalicular membrane and their relocation intracellularly. Quantitative colocalization analysis of Bsep and Mrp2 proteins revealed a steady decrease in the degree of colocalization and Mrp2 expression, indicating that although the properties of both transporters are affected, Mrp2 is altered more. These findings provide evidence that ethanol alters Bsep and Mrp2 canalicular transporters in the rat liver, at both the mRNA and protein levels. Mrp2 shows deeper involvement. Eight weeks appears to be a critical time point in this process.

Keywords

Ethanol Liver Bsep Mrp2 Quantitative colocalization analysis 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Vadim Zinchuk
    • 1
  • Olga Zinchuk
    • 2
  • Kunihiro Akimaru
    • 3
  • Fumio Moriya
    • 4
  • Teruhiko Okada
    • 1
  1. 1.Department of Anatomy and Cell BiologyKochi University Faculty of MedicineKochiJapan
  2. 2.Department of OphthalmologyKochi University Faculty of MedicineKochiJapan
  3. 3.Department of Environmental and Occupational HealthKochi University Faculty of MedicineKochiJapan
  4. 4.Department of Legal MedicineKochi University Faculty of MedicineKochiJapan

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