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Disruption of Polarized Function in Hepatocytes

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Toxicology - From Cells to Man

Part of the book series: Archives of Toxicology ((TOXICOLOGY,volume 18))

Abstract

Liver parenchymal epithelial cells (hepatocytes) are highly polarized in terms of both transport systems and intercellular communication (Handler, 1989; Figure 1).

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References

  • Akerboom T, Bultmann T and Helmet S (1988) Inhibition of biliary taurocholate excretion during menadione metabolism in perfused rat liver. Arch Biochem Biophys 263 , 10–18

    Article  PubMed  CAS  Google Scholar 

  • Azri S, Gandolfi AJ and Brendel K (1990). Precision-cut liver slices: an “in vitro ” system for profiling poential hepatotoxicants. In Vitro Toxicol 3 309 320

    Google Scholar 

  • Ballatori N and Truong AT (1989) Altered hepatic junctional permeability, bile acid excretion and glutathione efflux during oxidant challenge. J Pharmacol Exp Ther 251 1069–1075

    PubMed  CAS  Google Scholar 

  • Beer DG, Neveu MJ, Paul DL, Rapp UR and Pitot HC (1988) Expression of the c-raf proto oncogene, g-glutamyltranspeptidase, and gap junction protein in rat liver neoplasms. Cancer Res 48 1610–1617

    PubMed  CAS  Google Scholar 

  • Chipman JK (1995) Connexin genes as tumour suppressor genes? “Toxicology Elsewhere” Human Exptl Toxicol 14 539–540

    CAS  Google Scholar 

  • Feldmann G (1989) The cytoskeleton of the hepatocyte. J Hepatol 8 380–386

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald DJ, Mesnil M, Oyamada M, Tsuda H, Ho N and Yamasaki M (1989) Changes in gap junction protein (connexin 32) gene expression during rat liver carcinogenesis. J Cell Biochem 41 97–102

    Article  PubMed  CAS  Google Scholar 

  • Gant TW, Ramakrishna Rao DN, Mason RP and Cohen GM (1988) Redox cycling and sulphydryl arylation; their relative importance in the mechanism of quinone cytotoxicity to isolated hepatocytes. Chem Biol Interac 65 157–173

    Article  CAS  Google Scholar 

  • Gautam A, Ng O-C and Boyer JL (1987) Isolated rat hepatocyte couplets in short-term culture: structural characteristics and plasma membrane reorganisation. Hepatology 7 216–223

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez FJ and Gelboin HV (1994) Role of human cytochromes P450 in the metabolic activation of chemical carcinogens and toxins. Drug Metab Revs 26 165–183

    Article  CAS  Google Scholar 

  • Graf J, Gautam A and Boyer JL (1984) Isolated rat hepatocyte couplets: a primary secretory unit for electrophysiological studies of bile secretory function. Proc Natl Acad Sci USA 81 6516–6520

    CAS  Google Scholar 

  • Graf J and Boyer JL (1990) The use of isolated rat hepatocyte couplets in hepatobiliary physiology. J Hepatol 10 387–394

    Article  PubMed  CAS  Google Scholar 

  • Guppy MJ, Wilton JC, Sharma R, Coleman R and Chipman JK (1994) Modulation of phenobaritone-induced loss of gap junctional intercellular communication in hepatocyte couplets. Carcinogenesis 15 1917–1921

    Article  PubMed  CAS  Google Scholar 

  • Handler JS (1989) Overview of epithelial polarity. Annu Rev Physiol 51 729–740

    Article  PubMed  CAS  Google Scholar 

  • Jirtle RL, Handkins GR, Reisenbichler H and Boyer IJ (1994) Regulation of mannose 6- phosphate/insulin-like growth factor II receptors and transforming factors b during liver tumour promotion with phenobarbital. Carcinogenesis 15 1473–1478

    Article  PubMed  CAS  Google Scholar 

  • Jirtle RL, Meyer SA and Brockenbrough JS (1991) Liver tumour promoter phenobarbital: a biphasic modulator of hepatocyte proliferation. In: Chemically induced Cell proliferation: Implications for Risk Assessment. Wiley-Liss pp 209–216

    Google Scholar 

  • Jongen WMF, Fitzgerald DJ, Asamoto M, Piccoli C, Slaga TJ, Gros D, Takeichi M and Yamasaki H (1991) Regulation of connexin 43-mediated gap junctional intercellular communication by Ca++ in mouse epidermal cells is controlled by E-cadherin. J Cell Biol 114 545–555

    Article  PubMed  CAS  Google Scholar 

  • Kan KS and Coleman R (1988) The calcium ionophore A23187 increases the tight- junctional permeability in rat liver. Biochem J 256 1039–1041

    PubMed  CAS  Google Scholar 

  • Kawahara H, Marceau N and French SW (1989) Effects of agents which rearrange the cytoskeleton in vitro on the structure and function of hepatocyte canaliculi. Lab nvest 60 692–704

    CAS  Google Scholar 

  • Krutovskikh V.A., Mesnil M., Mazzoleni G and Yamasaki H. (1995) Inhibition of rat liver gap junction intercellular communication by tumor-promoting agents in vivo . Lab. Invest. 72 571–577

    PubMed  CAS  Google Scholar 

  • Lankester DJ. Chipman JK, Coleman R and Chenery RJ (1994a) Modelling of biliary excretion by metabolism and accumulation studies in hepatocyte couplets. Br J Clin Pharmacol 38 170–171

    Google Scholar 

  • Lankester DJ, Paul F, Chenery R, Coleman R and Chipman JK (1994b) Flow cytometric analysis of biliary excretion of cholyl-lysyl-fluorescein in rat hepatocyte couplets. Abstract B15. 14th European Drug Metabolism Workshop

    Google Scholar 

  • Leibold E and Schwarz LR (1993) Inhibition of intercellular communication in rat hepatocytes by phenobarbital, l,l,l-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT) and hexachlorocyclohexane (lindane): modification by antioxidants and inhibitors of cyclooxygenase. Carcinogenesis 14 2377–2382

    Article  PubMed  CAS  Google Scholar 

  • Leibold E, Greim H and Schwarz LR (1994) Inhibition of intercellular communication of rat hepatocytes by nafenopin: involvement of protein kinase C. Carcinogenesis 15 1265–1269

    Article  PubMed  CAS  Google Scholar 

  • Lieber CS (1984) Alcohol and the liver: 1984 update Hepatology 4 1243–1260

    Article  PubMed  CAS  Google Scholar 

  • Lowe PJ, Miyai K, Steinbach JH and Hardison WGM (1988) Hormonal regulation of hepatocyte tight junctional permeabilty. Am J Physiol 255 G454–G461

    PubMed  CAS  Google Scholar 

  • Lowenstein WR and Rowe B (1992) The cell-cell channel in the control of growth. Seminars Cell Biol 3 59–79

    Google Scholar 

  • Madara JL, Barenberg D and Carlson S (1986) Effects of cytochalasin D on occluding junctions of intestinal absorptive cells: Further evidence that the cytoskeleton may influence paracellular permeability and junctional charge selectivity. J Cell Biol 102 2125–2136

    Article  PubMed  CAS  Google Scholar 

  • Mesnil M, Fitzgerald DJ and Yamasaki H (1988) Phenobarbital specifically reduces gap junction protein mRNA level in rat liver. Mol Carcinog 1 79–81

    Article  PubMed  CAS  Google Scholar 

  • Mesnil M, Piccoli C and Yamasaki H (1993) An improved long-term culture of rat hepatocytes to detect liver tumour-promoting agents: results with phenobarbital. Eur J Pharmacol 24 59–66

    Google Scholar 

  • Mirabelli F, Salis A, Marinoni V, Finardi G, Bellomo G, Thor H and Orrenius S (1988) Menadione-induced bleb formation in hepatocytes is associated with the oxidation of thiol groups in actin. Arch Biochem Biophys 264 261–269

    Article  PubMed  CAS  Google Scholar 

  • Naramoto A, Ohno S, Kiyoshi F, Itoh N, Nakazawa K, Nakamo M and Shigematsu H (1991) Ultrastructural studies in hepatocyte cytoskeletons of phalloidin-treated rats by quick-freezing and deep-etching method. Hepatology 13 222–229

    Article  PubMed  CAS  Google Scholar 

  • Nathanson MH, Gautam A and Boyer JL (1990) Effects of vasopressin and phorbol dibutyrate on bile secretion in isolated rat hepatocyte couplets (Abstract). Gastroenterology 98 A615

    Google Scholar 

  • Nathanson MH and Boyer JL (1991) Mechanisms and regulation of bile secretion. Hepatology 14 551–569

    Article  PubMed  CAS  Google Scholar 

  • Neveu MJ, Babcock KL, Hertzberg EL, Paul DL, Nicholson BJ and Pitot HC (1994a) Colocalized alterations in connexin 32 and cytochrome P450 HB1/2 by phenobarbital and related liver tumour promoters. Cancer Res 54 , 3145–3152

    CAS  Google Scholar 

  • Neveu MJ, Hully JR, Babcock KL, Hertzberg EL, Nicholson BJ, Paul DL and Pitot HC (1994b) Multiple mechanisms are responsible for altered expression of gap junction genes during oncogenesis in rat liver. J Cell Science 107 83–95

    CAS  Google Scholar 

  • Neveu MJ, Hully JR, Paul DL and Pitot HC (1990) Reversible alteration in the expression of the gap junctional protein connexin 32 during tumour promotion in rat liver and its role during cell proliferation. Cancer Commun 2 21–31

    PubMed  CAS  Google Scholar 

  • Oshio C and Phillips MJ (1981) Contractility of bile canaliculi: implications for liver function. Science 212 1041–1042

    Article  PubMed  CAS  Google Scholar 

  • Paine AJ (1990) The maintenance of cytochrome P450 in rat hepatocyte culture; some applications of liver cell cultures to the study of drug metabolism, toxicity and the induction of the P450 system. Chem-Biol Interact 74 1–31

    Article  PubMed  CAS  Google Scholar 

  • Phillips MJ, Oshio C, Miyiari M and Smith CR (1983) Intrahepatic cholestasis as a canalicular motility disorder. Evidence using cytochalasin. Lab Invest 48 , 205–211

    PubMed  CAS  Google Scholar 

  • Pitot HC, Dragan Y, Sargent and Xu Y-H (1991) Biochemical markers associated with the stages of promotion and progression during hepatocarcinogenesis in the rat. Env Health Perspect 93 181–189

    CAS  Google Scholar 

  • Roman ID and Coleman R (1994) Disruption of canalicular function in isolated rat hepatocyte couplets caused by cyclosporin A. Biochemical Pharmacology 48 , 2181–2188

    Article  PubMed  CAS  Google Scholar 

  • Ruch RJ and Klaunig JE (1988) Kinetics of phenobarbital inhibition of intercellular communication in mouse hepatocytes. Cancer Res 48 2519–2523

    PubMed  CAS  Google Scholar 

  • Saez JC, Conner JA, Spray DC and Bennett MVL (1989) Hepatocyte gap junctions are permeable to a second messenger, inositol 1,4,5-triphosphate and to calcium ions. Proc Natl Acad Sci USA 86 2708–2712

    CAS  Google Scholar 

  • Schneeberger EE and Lynch RD (1992) Structure, function and regulation of cellular tight junctions. Am Physiol Soc L647–L661

    Google Scholar 

  • Schulte-Hermann R, Timmermann-Trosiener I, Barthel G and Bursch W (1990) DNA synthesis apoptosis and phenotypic expression as determinants of growth of altered foci in rat liver during phenobarbital promotion. Cancer Res 50 5127–5135

    PubMed  CAS  Google Scholar 

  • Seglen PO (1976) Preparation of isolated rat liver cells. Methods Cell Biol XIII 29–83

    Article  Google Scholar 

  • Spray DC, Ginzberg RD, Morales EA, Gatmaitan Z and Arias IM (1986) Electrophysiological properties of gap junctions between dissociated pairs of rat hepatocytes. J Cell Biol 103 135–144

    Article  PubMed  CAS  Google Scholar 

  • Stone V, Coleman R and Chipman JK (1995) Comparison of the effects of redox cycling and arylating quinones on hepatobiliary function and glutathione homeostasis in rat hepatocyte couplets. Toxicol Apppl Pharmacol . In Press

    Google Scholar 

  • Stone V, Johnson GD, Wilton JC, Coleman R and Chipman JK (1994) Effect of oxidative stress and disruption of Ca++ homeostasis on hepatocyte canalicular function in vitro . Biochem Pharmacol 47 625–632

    Article  PubMed  CAS  Google Scholar 

  • Takeguchi N, Ichimura K, Koike M, Matsui W, Kashiwagura T and Kawahara K (1993) Inhibition of the mutlidrug efflux pump in isolated hepatocyte couplets by immunosuppressants FK506 and cyclosporins Transplantation 55 646–650

    Article  PubMed  CAS  Google Scholar 

  • Thibault N, Claude JR and Ballet F (1992) Actin filament alteration as a potential marker for cholestasis: a study in isolated rat hepatocyte couplets. Toxicology 73 269–279

    Article  PubMed  CAS  Google Scholar 

  • Thor H, Mirabelli F, Salis A, Cohen GM, Bellomo G and Orrenius S (1988) Alterations in hepatocyte cytoskeleton caused by redox cycling and alkylating quinones. Arch Biochem Biophys 266 397–407

    Article  PubMed  CAS  Google Scholar 

  • Trosko JE, Chang CC, Madhukar BV and Oh SY (1990). Modulators of gap junction function: the scientific basis of epigenetic toxicology. In Vitro Toxicol 3 9–26

    CAS  Google Scholar 

  • Tsuda H, Lee G and Farber E (1980) Induction of resistant hepatocytes as a new principle for a possible short term test for carcinogens. Cancer Res 40 1157–1164

    PubMed  CAS  Google Scholar 

  • Watanabe N, Tsukada N, Smith CR, Edwards V and Phillips MJ (1991) Permeabolised hepatocyte couplets. Adenosine triphosphate-dependent bile canalicular contractions and a circumferential pericanalicular microfilament belt demonstrated. Lab Invest 65 203–213

    PubMed  CAS  Google Scholar 

  • Watanabe S, Smith CR and Phillips MJ (1985) Coordination of the contractile activity of bile canaliculi: evidence from calcium microinjection of triplet hepatocytes. Lab Invest 53 275–279

    PubMed  CAS  Google Scholar 

  • Wilton JC, Matthews GM, Burgoyne RD, Mills CO, Chipman JK and Coleman R (1994) Fluorescent choleretic and cholestatic bile salts take different paths across the hepatocyte: transcytosis of glycolithocholate leads to an extensive redistribution of annexin II. J Cell Biol 127 401–410

    Article  PubMed  CAS  Google Scholar 

  • Wilton JC, Chipman JK, Lawson CJ, Strain AJ and Coleman R (1993) Periportal and perivenous-enriched hepatocyte couplets: differences in canalicular activity and in response to oviduthe stress. Biochem J 292 773–779

    PubMed  CAS  Google Scholar 

  • Yamasaki H (1991) Aberrant expression and function of gap junctions during carcinogenesis. Environ Hlth Perspect 93 191–197

    Article  CAS  Google Scholar 

  • Yi W, Zhao Y and Chou I-N (1987) Paraquat-induced cytoskeletal injury in cultured cells. Toxicol Appl Pharmacol 91 96–106

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. School of Biochemistry, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    J. K. Chipman, R. Coleman, J. C. Wilton, M. J. Guppy, V. Stone & D. J. Lankester

Authors
  1. J. K. Chipman
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  2. R. Coleman
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  3. J. C. Wilton
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  4. M. J. Guppy
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  5. V. Stone
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  6. D. J. Lankester
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Editor information

Editors and Affiliations

  1. Interkantonale Kontrollstelle für Heilmittel, Erlachstrasse 8, CH-3000, Bern 9, Switzerland

    Jürg P. Seiler

  2. Department of Pharmacology, Charles University of Prague, 3rd Medical School, Ruská 87, Czech Republic

    Olga Kroftová

  3. Department of Pharmacology, Charles University, Faculty of Medicine, Karlovarská 48, CZ-30166, Pilsen, Czech Republic

    Vladislav Eybl

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© 1996 Springer-Verlag Berlin Heidelberg

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Chipman, J.K., Coleman, R., Wilton, J.C., Guppy, M.J., Stone, V., Lankester, D.J. (1996). Disruption of Polarized Function in Hepatocytes. In: Seiler, J.P., Kroftová, O., Eybl, V. (eds) Toxicology - From Cells to Man. Archives of Toxicology, vol 18. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61105-6_13

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  • DOI: https://doi.org/10.1007/978-3-642-61105-6_13

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64696-6

  • Online ISBN: 978-3-642-61105-6

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