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Changes in GM1 ganglioside content and localization in cholestatic rat liver

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Abstract

(Glyco)sphingolipids (GSL) are believed to protect the cell against harmful environmental factors by increasing the rigidity of plasma membrane. Marked decrease of membrane fluidity in cholestatic hepatocytes was described but the role of GSL therein has not been investigated so far. In this study, localization in hepatocytes of a representative of GSL, the GM1 ganglioside, was compared between of rats with cholestasis induced by 17α-ethinylestradiol (EE) and vehicle propanediol treated or untreated animals. GM1 was monitored by histochemical reaction employing cholera toxin B-subunit. Our findings in normal rat liver tissue showed that GM1 was localized in sinusoidal and canalicular hepatocyte membranes in both peripheral and intermediate zones of the hepatic lobules, and was nearly absent in central zones. On the contrary, in EE-treated animals GM1 was also expressed in central lobular zones. Moreover, detailed densitometry analysis at high magnification showed greater difference of GM1 expression between sinusoidal surface areas and areas of adjacent cytoplasm, caused as well by increased sinusoidal staining in central lobular zone as by decreased staining in cytoplasm in peripheral zone. These differences correlated with serum bile acids as documented by linear regression analyses. Both GM1 content and mRNA corresponding to GM1-synthase remained unchanged in livers; the enhanced expression of GM1 at sinusoidal membrane thus seems to be due to re-distribution of cellular GM1 at limited biosynthesis and could be responsible for protection of hepatocytes against harmful effects of bile acids accumulated during cholestasis.

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Abbreviations

ALP:

alkaline phosphatase

BSA:

bovine serum albumin

EE:

17α-ethinylestradiol

PD:

1,2-propanediol

GSL:

glycosphingolipids

PBS:

phosphate buffer saline

TBA:

total bile acids

 :

Ganglioside symbols, according to Svennerholm [26, 27], with IUPAC-IUB [28] nomenclature in parentheses

GM3:

(II3NeuAc-LacCer)

GM2:

(II3NeuAc-GgOse3Cer)

GM1:

(II3NeuAc-GgOse4Cer)

GD3:

(II3(NeuAc)2-Lac-Cer)

GD2:

(II3(NeuAc)2-GgOse3Cer)

GD1a:

(IV3NeuAc,II3NeuAcGgOse4Cer)

GD1b:

(II3(NeuAc)2-GgOse4Cer)

GT1b:

(IV3NeuAc,II3(NeuAc)2-GgOse4Cer)

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Acknowledgements

We thank Marie Zadinová and Martin Leníček for their help with animal experiments and Alena Veselá and Ladislav Trnka for their excellent technical assistance. This work was supported by the Internal Grant Agency of the Ministry of Health of the Czech Republic, Project No. 8079-3.

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Authors and Affiliations

  1. Institute of Histology and Embryology, Prague, Czech Republic

    Marie Jirkovská & Jaroslava Šmídová

  2. Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, U Nemocnice 2, 128 08, Prague 2, Czech Republic

    Filip Majer, Libor Vítek & František Šmíd

  3. 4th Department of Internal Medicine, Prague, Czech Republic

    Libor Vítek

  4. General Military Hospital, Prague, Czech Republic

    Zdeněk Mareček

  5. Institute of Pathology, 1st Medical Faculty, Charles University, Prague 2, Czech Republic

    Jan Stříteský

  6. Department of Signal Transduction, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague 4, Czech Republic

    Gouse Mohiddin Shaik & Petr Dráber

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  1. Marie Jirkovská
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Correspondence to František Šmíd.

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Jirkovská, M., Majer, F., Šmídová, J. et al. Changes in GM1 ganglioside content and localization in cholestatic rat liver. Glycoconj J 24, 231–241 (2007). https://doi.org/10.1007/s10719-007-9030-7

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  • DOI: https://doi.org/10.1007/s10719-007-9030-7

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