Changes in GM1 ganglioside content and localization in cholestatic rat liver |
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Authors: | Marie Jirkovská Filip Majer Jaroslava Šmídová Jan Stříteský Gouse Mohiddin Shaik Petr Dráber Libor Vítek Zdeněk Mareček František Šmíd |
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Institution: | (1) Institute of Histology and Embryology, Prague, Czech Republic;(2) Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, U Nemocnice 2, 128 08 Prague 2, Czech Republic;(3) 4th Department of Internal Medicine, Prague, Czech Republic;(4) General Military Hospital, Prague, Czech Republic;(5) Institute of Pathology, 1st Medical Faculty, Charles University, Prague 2, Czech Republic;(6) Department of Signal Transduction, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague 4, Czech Republic |
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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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Keywords: | Cholestasis Ethinylestradiol Hepatocyte Cholera toxin Gangliosides |
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