Skip to main content
Log in

The Involvement of Altered Vesicle Transport in Redistribution of Ca2+, Mg2+-ATPase in Cholestatic Rat Liver

  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Abstract

Vectorial sorting of plasma membrane protein-containing vesicles is essential for the establishment and maintenance of cell polarity. In the present study, the involvement of altered vesicle transport in the redistribution of membrane-bound Ca2+, Mg2+-ATPase resulting from cholestasis was investigated in hepatocytes. Cholestasis was induced in rat liver by common bile duct ligation. Ca2+, Mg2+-ATPase activity was demonstrated histochemically at the light and electron microscopical levels. Microtubules, an important factor for transcellular transport of vesicles, were studied in situ by immunofluorescence microscopy and electron microscopy in detergent-extracted preparations. The results showed that microtubules underwent significant changes after common bile duct ligation. The most pronounced alteration was focal accumulation of β-tubulin in the cytoplasm of hepato cytes after 7 days of common bile duct ligation. At the electron microscopical level, the number of microtubules was increased considerably. In control livers, the activity of Ca2+, Mg2+-ATPase was localized only at the apical plasma membrane of hepatocytes, but it was also present at the basolateral plasma membrane after common bile duct ligation. The number of intracellular vesicles containing Ca2+, Mg2+-ATPase activity was increased strikingly, and some of them were associated with lateral membrane domains in which Ca2+, Mg2+-ATPase activity was found. It is concluded that common bile duct ligation induces the rearrangement of microtubules, which may disturb vectorial transport of Ca2+, Mg2+-ATPase-containing vesicles in hepatocytes, leading to the redistribution of Ca2+, Mg2+-ATPase. © 1998 Chapman & Hall

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Achler, C., Filmer, D., Merte, C. & Drenckhahn, D. (1989) Role of microtubules in polarized delivery of apical membrane proteins to the brush border of the intestinal epithelium. J. Cell Biol. 109, 179-89.

    Google Scholar 

  • Araki, N., Lee, T., Matsubara, H. & Takashima, Y. (1993a) An improved technique for observation both membranous organelles and cytoskeleton in saponinextracted cells. J. Electron Microsc. 42, 51-4.

    Google Scholar 

  • Araki, N., Ohno, J., Lee, T., Takashima, Y. & Ogawa, K. (1993b) Nematolysosomes (elongated lysosomes) in rat hepatocytes: their distribution, microtubule dependence, and role in the endocytotic transport pathway. Exp. Cell Res. 204, 18-91.

    Google Scholar 

  • Araki, N., Takashima, Y. & Makita, T. (1995) Redistribution and fate of colchicines-induced alkaline phosphatase in rat hepatocytes: possible formation of autophagosomes whose membrane is derived from excess plasma membrane. Histochem. Cell Biol. 104, 257-65.

    Google Scholar 

  • Aronson, D.C., De Haan, J., James, J., Bosch, K.S., Ketel, A.G., Houtkooper, J.M. & Heijmans, H.S.A. (1988) Quantitative aspects of the parenchyma-stroma relationship in experimentally induced cholestasis. Liver 8, 116-26.

    Google Scholar 

  • Barr, V.A. & Hubbard, A.L. (1993) Newly synthesized hepatocyte plasma membrane proteins are transported in transcytotic vesicles in the bile duct-ligated rat. Gastroenterology 105, 554-71.

    Google Scholar 

  • Bartles, J.R., Feracci, H.M., Stieger, B. & Hubbard, A.H. (1987) Biogenesis of the rat hepatocyte plasma membrane in vivo: comparison of the pathways taken by apical and basolateral proteins using subcellular fractionation. J. Cell Biol. 105, 1241-51.

    Google Scholar 

  • De Almeida, B.J. & Stow, J.L. (1991) Disruption of microtubules alters polarity of basement membrane proteoglycan secretion in epithelial cells. Am. J. Physiol. 260, C691-C700.

    Google Scholar 

  • Desmet, V. J. (1987) Cholestasis: extrahepatic obstruction and secondary biliary cirrhosis. In Pathology of the Liver (edited by R.N.M. MacSwee, P.P. Anthony and P.J. Scheuer), pp. 364-413. London: Churchill Livingstone.

    Google Scholar 

  • Drenckhahn, D., Jons, T., Kollert–Jons, A., Koob, R., Kraemer, D. & Wagner, S. (1993) Cytoskeleton and epithelial polarity. Ren. Physiol. Biochem. 16, 6-14.

    Google Scholar 

  • Durand-schneider, A.M., Maurice, M., Dumont, M. & Feldmann, G. (1987) Effect of colchicine and phalloidin on the distribution of three plasma membrane antigens in rat hepatocytes: comparison with bile duct ligation. Hepatology 7, 1239-48.

    Google Scholar 

  • Durand-schneider, A.M., Bouanga, J.C., Feldmann, G. & Maurice, M. (1991) Microtubule disruption interferes with the structural and functional integrity of the apical pole in primary cultures of rat hepatocytes. Eur. J. Cell Biol. 56, 260-8.

    Google Scholar 

  • Fath, K.R., Mamajiwalla, S.N. & Burgess, D.R. (1993) The cytoskeleton in development of epithelial cell polarity. J. Cell Sci. 17 (Suppl.), 65-73.

    Google Scholar 

  • Frederiks, W.M., Van Noorden, C. J.F., Aronson, D.C., Marx, F., Bosch, K.S., Jonges, G.N., Vogels, I.M.C. & James, J. (1990) Quantitative changes in acid phosphatase, alkaline phosphatase and 59-nucleotidase activity in rat liver after experimentally induced cholestasis. Liver 10, 158-66.

    Google Scholar 

  • Gloushankova, N.A., Lyubimova, A.V., Tint, I.S., Feder, H.H., Vasiliev, J.M. & Gelfand, I.M. (1994) Role of the microtubular system in morphological organization of normal and oncogene-transfected epithelial cells. Proc. Natl. Acad. Sci. USA 91, 8597-601.

    Google Scholar 

  • Hammerton, R.W., Krzeminski, K.A., Mays, R.W., Ryan, T.A., Wollner, D.A. & Nelson, W.J. (1991) Mechanism for regulating cell surface distribution of Na+, K+-ATPase in polarized epithelial cells. Science 254, 847-50.

    Google Scholar 

  • Hubbard, A.L. & Stieger, B. (1989) Involvement of microtubules in the transport of bile canalicular proteins from basolateral to the apical plasma membrane domain in rat hepatocytes. J. Cell Biol. 107, 447a.

    Google Scholar 

  • Hubbard, A.L., Bartles, J.R. & Braiterman, L.T. (1985) Identification of rat hepatocyte plasma membrane proteins using monoclonal antibodies. J. Cell Biol. 100, 1115-25.

    Google Scholar 

  • Hubbard, A.L., Stieger, B. & Bartles, J.R. (1989) Biogenesis of endogenous plasma membrane proteins in epithelial cells. Annu. Rev. Physiol. 51, 755-70.

    Google Scholar 

  • Kaplan, M.M., Ohkubo, A., Quaroni, E.G. & Sze-tu, D. (1983) Increased synthesis of rat liver alkaline phosphatase by bile duct ligation. Hepatology 3, 368-76.

    Google Scholar 

  • Le gall, A.H., Yeaman, C., Muesch, A. & Rodriguezboulan, E. (1995) Epithelial cell polarity: new perspectives. Semin. Nephrol. 15, 272-84.

    Google Scholar 

  • Lin, S.H. (1988) Two Ca++-dependent ATPases in rat liver plasma membrane. The previously purified (Ca++-Mg++)-ATPase is not a Ca++-pump but an ecto-ATPase. J. Biol. Chem. 263, 12253-8.

    Google Scholar 

  • Lin, S.H. (1989) Localization of the ecto-ATPase (ectonucleotidase) in the rat hepatocyte plasma membrane. Implication for the functions of the ecto-ATPase. J. Biol. Chem. 264, 14403-7.

    Google Scholar 

  • Marks, D.L., Larusso, N.F. & Mcniven, M.A. (1995) Isolation of the microtubule-vesicle motor kinesin from rat liver: selective inhibition by cholestatic bile acids. Gastroenterology 108, 824-33.

    Google Scholar 

  • Meier, P.J. (1988) Transport polarity of hepatocytes. Semin. Liver Dis. 8, 293-307.

    Google Scholar 

  • Meier, P.J. (1993) Canalicular membrane transport processes. In Hepatic Transport and Bile Secretion: Physiology and Pathophysiology (edited by N. Tavoloni and P.D. Berk), pp. 587-96. New York: Raven Press.

    Google Scholar 

  • Meier, P.J., Sztul, E.S., Reuben, A. & Boyer, J.L. (1984) Structural and functional polarity of canalicular and basolateral plasma membrane vesicles isolated in high yield from rat liver. J. Cell Biol. 98, 991-1000.

    Google Scholar 

  • Misek, D.E., Bard, E. & Rodriguez-boulan, E.J. (1984) Biogenesis of epithelial cell polarity: intracellular sorting and vectorial exocytosis of an apical plasma membrane glycoprotein. Cell 39, 537-46.

    Google Scholar 

  • Novikoff, P.M., Cammer, M., Tao, L., Oda, H., Stockert, R.J., Wolkoff, A.W. & Satir, P. (1996) Threedimensional organization of rat hepatocyte cytoskeleton: relation to the asialoglycoprotein endocytosis pathway. J. Cell Sci. 109, 21-32.

    Google Scholar 

  • Ojakian, G.K. & Schwimmer, R. (1992) Antimicrotubule drugs inhibit the polarized insertion of an intracellular glycoprotein pool into the apical membrane of Madin–Darby canine kidney (MDCK) cells. J. Cell Sci. 103, 677-87.

    Google Scholar 

  • Sakisaka, S., Cheng, O. & Boyer, J.L. (1988) Tubulovesicular transcytotic pathway in isolated rat hepatocyte couplets in culture. Effect of colchicine and taurocholate. Gastroenterology 95, 793-804.

    Google Scholar 

  • Schell, M. J., Maurice, M., Stieger, B. & Hubbard, A.L. (1992) 59-Nucleotidase is sorted to the apical domain of hepatocytes via an indirect route. J. Cell Biol. 119, 1173-82.

    Google Scholar 

  • Sippel, C.J., Anathanarayanan, M. & Suchy, F.J. (1990) Isolation and characterization of the canalicular membrane bile acid transport protein of rat liver. Am. J. Physiol. 258, G728-G737.

    Google Scholar 

  • Sippel, C.J., Suchy, F.J., Anathanarayanan, M. & Perlmutter, D.H. (1993) The rat liver ecto-ATPase is also a canalicular bile acid transport protein. J. Biol. Chem. 268, 2083-91.

    Google Scholar 

  • Sippel, C.J., Mccollum, M.J. & Perlmutter, D.H. (1994) Bile acid transport by the rat liver canalicular bile acid transport/ecto-ATPase protein is dependent on ATP but not on its own ecto-ATPase activity. J. Biol. Chem. 269, 2820-6.

    Google Scholar 

  • Song, J.Y., Van Marle, J., Van Noorden, C.J.F. & Frederiks, W.M. (1996) Redistribution of Ca++, Mg++-ATPase activity in relation to alterations of cytoskeleton and tight junctions in hepatocytes of cholestatic rat liver. Eur. J. Cell Biol. 71, 277-85.

    Google Scholar 

  • Stieger, B., Meier, P.J. & Landmann, L. (1994) Effect of obstructive cholestasis on membrane traffic and domain-specific expression of plasma membrane proteins in rat liver parenchymal cells. Hepatology 20, 201-12.

    Google Scholar 

  • Van Noorden, C.J.F. & Hulstaert, C.E. (1991) Electron microscopical enzyme histochemistry. In Electron Microscopy in Biology. Practical Approach (edited by J.R. Harris), pp. 125-49. Oxford: Oxford University Press.

    Google Scholar 

  • Warren, G. (1985) Membrane traffic and organelle division. Trends Biochem. Sci. 10, 439-43.

    Google Scholar 

  • Yokota, S. (1989) Effect of colchicine on the intracellular transport of secretory proteins in rat liver parenchymal cells. Immunocytochemical observation. Cell Struct. Funct. 14, 545-59.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, JY., Van Noorden, C.J.F. & Frederiks, W.M. The Involvement of Altered Vesicle Transport in Redistribution of Ca2+, Mg2+-ATPase in Cholestatic Rat Liver. Histochem J 30, 909–916 (1998). https://doi.org/10.1023/A:1003455608511

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1003455608511

Keywords

Navigation