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Experimental evidence that the physiological position of the liver within the circulation is not a major determinant of zonation of gene expression

1993; Lippincott Williams & Wilkins; Volume: 18; Issue: 5 Linguagem: Inglês

10.1002/hep.1840180521

1527-3350

Gerry T. M. Wagenaar, Robert A.F.M. Chamuleau, Jan G. de Haan, M.A.W. Maas, Piet A. J. de Boer, Frans Marx, Antoon F.M. Moorman, Wilma M. Frederiks, Wouter H. Lamers,

Liver Disease and Transplantation

HepatologyVolume 18, Issue 5 p. 1144-1153 Original ArticleFree Access Experimental evidence that the physiological position of the liver within the circulation is not a major determinant of zonation of gene expression Gerry T. M. Wagenaar, Gerry T. M. Wagenaar Department of Anatomy and Embryology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands Department of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorRobert A. F. M. Chamuleau, Robert A. F. M. Chamuleau Department of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorJan G. de Haan, Jan G. de Haan Department of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorMartinus A. W. Maas, Martinus A. W. Maas Department of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorPiet A. J. de Boer, Piet A. J. de Boer Department of Anatomy and Embryology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorFrans Marx, Frans Marx Laboratory of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorAntoon F. M. Moorman, Antoon F. M. Moorman Department of Anatomy and Embryology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorWilma M. Frederiks, Wilma M. Frederiks Laboratory of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorWouter H. Lamers M.D., Ph.D., Corresponding Author Wouter H. Lamers M.D., Ph.D. Department of Anatomy and Embryology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Anatomy and Embryology, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands===Search for more papers by this author Gerry T. M. Wagenaar, Gerry T. M. Wagenaar Department of Anatomy and Embryology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands Department of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorRobert A. F. M. Chamuleau, Robert A. F. M. Chamuleau Department of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorJan G. de Haan, Jan G. de Haan Department of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorMartinus A. W. Maas, Martinus A. W. Maas Department of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorPiet A. J. de Boer, Piet A. J. de Boer Department of Anatomy and Embryology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorFrans Marx, Frans Marx Laboratory of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorAntoon F. M. Moorman, Antoon F. M. Moorman Department of Anatomy and Embryology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorWilma M. Frederiks, Wilma M. Frederiks Laboratory of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsSearch for more papers by this authorWouter H. Lamers M.D., Ph.D., Corresponding Author Wouter H. Lamers M.D., Ph.D. Department of Anatomy and Embryology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Anatomy and Embryology, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands===Search for more papers by this author First published: November 1993 https://doi.org/10.1002/hep.1840180521Citations: 35AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Many enzymes are distributed heterogeneously within the liver lobule. The factors that play a determining role in the establishment and maintenance of these heterogeneous expression patterns have not yet been identified. To investigate whether the composition of the afferent hepatic blood plays a crucial role in the maintenance of the heterogeneity of gene expression of the parenchymal cells within the liver lobule, we changed the source of the afferent hepatic blood by microsurgical techniques. Three different groups of experimental animals were studied: rats with livers that are perfused with portal blood only (ligation of the hepatic artery), with caval blood only (portocaval transposition and ligation of the hepatic artery) and arterial blood only (portocaval shunt, arterialization of the distal end of the portal vein and ligation of the hepatic artery). To study differences in gene expression patterns, we chose enzymes that have a heterogeneous expression pattern within the liver lobule: the periportally located enzymes carbamoylphosphate synthase, succinate dehydrogenase, phosphoenolpyruvate carboxylkinase and the pericentrally located enzymes glutamine synthase, glutamate dehydrogenase and NADPH–cytochrome P-450 reductase. To eliminate the potential interference of the long half-lives of some of these proteins on the interpretation of the results, we also studied the distribution of the mRNAs of carbamoylphosphate synthase, glutamine synthase, glutamate dehydrogenase and phosphoenolpyruvate carboxykinase. The animals were studied 2 wk after the operations. On the basis of their changes in body weight the animals were in steady state for at least a week. The patterns of gene expression of the enzymes studied did not change, regardless of the source of the altered afferent hepatic blood. The changes in gene expression that were observed in animals that did not regain their preoperative weight were shown to be caused by a limited intake of food. This study demonstrates that the physiological position of the liver within the circulation (i.e., between the gastrointestinal tract and the systemic circulation) is not as critical as is often stated and is certainly not essential for the maintenance of liver cell heterogeneity. The data suggest that the direction of the bloodstream (i.e., the existence of an upstream and a downstream compartment) is a major determinant of zonation of gene expression. (HEPATOLOGY 1993;18:1144-1153). References 1 Gaasbeek Janzen JW, Moorman AFM, Lamers WH, Charles R. Development of the heterogeneous distribution of carbamoylphosphate synthetase (ammonia) in rat liver parenchyma during postnatal development. J Histochem Cytochem 1985; 339: 1205– 1211. 2 Gaasbeek Janzen JW, Gebhardt R, Ten Voorde CHJ, Lamers WH, Charles R, Moorman AFM. Heterogeneous distribution of glutamine synthetase during rat liver development. J Histochem Cytochem 1987; 35: 49– 54. 3 Lamers WH, Gaasbeek Janzen JW, Moorman AFM, Charles R, Knecht E, Martinez-Ramon A, Hernandez-Yago J, et al. Immunohistochemical localization of glutamate dehydrogenase in rat liver: plasticity of the distribution during development and with hormone treatment. J Histochem Cytochem 1988; 36: 41– 47. 4 Moorman AFM, de Boer PAJ, Geerts WJC, van de Zande LPWG, Charles R, Lamers WH. Complementary distribution of CPS (ammonia) and GS mRNA in rat liver acinus is regulated at a pretranslational level. J Histochem Cytochem 1988; 36: 751– 755. 5 Moorman AFM, Vermeulen JLM, Charles R, Lamers WH. Localization of ammonia metabolizing enzymes in human liver: ontogenesis of heterogeneity. HEPATOLOGY 1989; 9: 367– 372. 6 Gebhardt R. Metabolic zonation of the liver: regulation and implications for liver function. Pharmacol Ther 1992; 53: 275– 354. 7 Bartels H, Linnemann H, Jungermann K. Predominant localization of phosphoenolpyruvate carboxykinase mRNA in the periportal zone of rat liver parenchyma demonstrated by in situ hybridization. FEBS Lett 1989; 248: 188– 194. 8 Lamers WH, Gaasbeek Janzen JW, te Kortschot A, Charles R, Moorman AFM. The development of enzymic zonation in liver parenchyma is related to the development of the acinar architecture. Differentiation 1987; 35: 228– 235. 9 Moorman AFM, de Boer PAJ, Charles R, Lamers WH. Diet- and hormone-induced reversal of the carbamoylphosphate synthetase mRNA gradient in the rat liver lobulus. FEBS Lett 1990; 276: 9– 13. 10 Jungermann K, Katz N. Functional specialization of different hepatocyte populations. Physiol Rev 1989; 69: 708– 764. 11 Lamers WH, Been W, Charles R, Moorman AFM. Hepatocytes explanted in the spleen preferentially express carbamoylphosphate synthetase rather than glutamine synthetase. HEPATOLOGY 1990; 12: 701– 709. 12 Schöls L, Mecke D, Gebhardt R. Reestablishment of the heterogenous distribution of hepatic glutamine synthetase during regeneration after CCl4-intoxication. Histochemistry 1990; 94: 49– 54. 13 Schrode W, Mecke D, Gebhardt R. Induction of glutamine synthetase in periportal hepatocytes by cocultivation with a liver epithelial cell line. Eur J Cell Biol 1990; 53: 35– 41. 14 Hellkamp J, Christ B, Bastian H, Jungermann K. Modulation by oxygen of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocte cultures. FEBS Lett 1991; 198: 635– 639. 15 Christ B, Nath A, Jungermann K. Mechanism of the inhibition by insulin of the glucagon-dependent activation of the phospoenolpyruvate carboxykinase gene in rat hepatocyte cultures. Biol Chem Hoppe Seyler 1990; 371: 395– 402. 16 Gaasbeek Janzen JW, Lamers WH, Moorman AFM, de Graaf A, Los JA, Charles R. Immunohistochemical localization of carbamoylphosphate synthetase (ammonia) in adult rat liver. J Histochem Cytochem 1984; 32: 557– 564. 17 Frederiks WM, Marx F, Myagkaya GL. A histochemical study of changes in mitochondrial enzyme activities of rat liver after ischemia in vitro. Virchows Arch 1986; 51: 321– 329. 18 Gebhardt R, Mecke D. Heterogeneous distribution of glutamine synthetase among rat liver parenchymal cells in situ and in primary cultures. EMBO J 1983; 2: 567– 570. 19 Van Noorden CJF, Butcher RG. A quantitative histochemical study of NADPH-ferrihemoprotein reductase activity. Histochem J 1986; 18: 364– 370. 20 Hess F. Shunts in the portal area. In: R Marquet, F Hess, eds. Microsurgery: experimental techniques in the rat and clinical applications. Gent: European Press, 1976: 145– 163. 21 Lee SH, Fisher B. Portocaval shunt in the rat. Surgery 1961; 50: 668– 672. 22 Van Noorden CJF, Frederiks WM. Enzyme histochemistry: a laboratory manual of current methods. Oxford: Oxford University Press, 1992. 23 de Groot CJ, Ten Voorde CHJ, van Andel RE, te Kortschot A, Gaasbeek Janzen JW, Wilson RH, Moorman AFM, et al. Reciprocal regulation of glutamine synthetase and carbamoylphosphate synthetase levels in rat liver. Biochim Biophys Acta 1987; 908: 231– 240. 24 Charles R, de Graaf A, Moorman AFM. Radioimmunochemical determination of carbamoylphosphate synthetase (ammonia) content of adult rat liver. Biochim Biophys Acta 1980; 629: 36– 49. 25 Henderson C. Aminoalkylisane: an inexpensive, simple preparation for slide adhesion. J Histotechnol 1989; 12: 123– 124. 26 Moorman AFM, de Boer PAJ, Das AT, Labruyère WT, Charles R, Lamers WH. Expression patterns of mRNAs for ammoniametabolizing enzymes in the developing rat: the ontogenesis of hepatocyte heterogeneity. Histochem J 1990; 22: 457– 468. 27 van de Zande LPWG, Labruyère WT, Smaling MM, Moorman AFM, Wilson RH, Charles R, Lamers WH. Nucleotide sequence of rat GS mRNA. Nucleic Acids Res 1988; 16: 7726. 28 van de Zande L, Labruyère WT, Arnberg AC, Wilson RH, Van Den Bogaert AJW, Das AT, van Oorschot DAJ, et al. Isolation and characterization of the rat glutamine synthetase–encoding gene. Gene 1990; 87: 225– 232. 29 de Groot CJ, Zonneveld D, de Laaf RTM, Dingemanse MA, Mooren PG, Moorman AFM, Lamers WH, et al. Developmental and hormonal regulation of carbamoylphosphate synthetase gene expression in rat liver: evidence for control mechanisms at different levels in the perinatal period. Biochim Biophys Acta 1986; 866: 61– 67. 30 Das AT, Moerer P, Charles R, Moorman AFM, Lamers WH. Nucleotide sequence of rat liver glutamate dehydrogenase cDNA. Nucleic Acids Res 1989; 17: 2355. 31 Yoo-Warren H, Monahan JE, Short J, Short H, Bruzel A, Wynshaw-Boris A, Meisner HM, et al. Isolation and characterization of the gene coding for cytosolic phosphoenolpyruvate carboxykinase (GTP) from the rat. Proc Natl Acad Sci USA 1983; 80: 3656– 3660. 32 Nicoletti M, Gueri C, Grisolia S. Turnover of carbamoylphosphate synthetase, of other mitochondrial enzymes and of rat tissues. Eur J Biochem 1977; 75: 583– 592. 33 Bartels H, Herbort H, Jungermann K. Predominant periportal expression of the phosphoenolpyruvate carboxykinase and tyrosine aminotransferase genes in rat liver: dynamics during the daily feeding rhythm and starvation-refeeding demonstrated by in situ hybridization. Histochemistry 1990; 95: 637– 644. 34 Lamers WH, Hoynes KE, Zonneveld D, Moorman AFM, Charles R. Noradrenergic innervation of developing rat liver: its relation to the development of the liver architecture and enzymic zonation. Anat Embryol 1988; 178: 175– 181. 35 Nolan EM, Masters JN, Dunn A. Growth hormone regulation of hepatic glutamine synthetase mRNA levels in rats. Mol Cell Endocrinol 1990; 69: 101– 110. 36 Arias IM, Jakoby WB, Popper H, Schachter D, Shafritz DA. Introduction, organizational principles. In: IM Arias, WB Jakoby, H Popper, D Schachter, DA Shafritz, eds. The liver: biology and pathobiology. Vol 2. New York: Raven Press, 1988: 1– 6. Citing Literature Volume18, Issue5November 1993Pages 1144-1153 ReferencesRelatedInformation