Zonation of metabolism and gene expression in liver

ConclusionThe zonation of gene expression resulting in the different cellular equipment of liver cells with enzymes, translocators and subcellular structures is regulated mainly at a pretranslational level. In the dynamic zonation of carbohydrate metabolizing enzymes, gradients in oxygen and in the glucagon/insulin ratio decreasing from the periportal to the perivenous area appear to be major effectors. In the stable zonation of ammonia-metabolizing enzymes local paracrine cell-cell interactions via diffusible mediators could play a major role (Fig. 6).

[1]  D. Sasse,et al.  Liver architecture. , 1992, Enzyme.

[2]  A. Novikoff,et al.  CELL HETEROGENEITY WITHIN THE HEPATIC LOBULE OF THE RAT (STAINING REACTIONS) , 1959, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[3]  D. Sasse,et al.  The intra-acinar distribution patterns of alcohol-dehydrogenase activity in the liver of juvenile, castrated and testosterone-treated rats. , 1987, Biological chemistry Hoppe-Seyler.

[4]  M. Goldberg,et al.  Regulatory elements of the erythropoietin gene. , 1991, Blood.

[5]  K. Jungermann,et al.  Distribution of cyclic AMP phosphodiesterase in microdissected periportal and perivenous rat liver tissue with different dietary states , 2004, Histochemistry.

[6]  K. Jungermann,et al.  Integration of function in the hepatic acinus: intercellular communication in neural and humoral control of liver metabolism. , 1994, Progress in liver diseases.

[7]  B. Corrin,et al.  The pattern of glycogen distribution in the liver. , 1968, American Journal of Anatomy.

[8]  K. Jungermann,et al.  Long-term effects of physiological oxygen concentrations on glycolysis and gluconeogenesis in hepatocyte cultures. , 1985, European journal of biochemistry.

[9]  J. A. Los,et al.  Immunohistochemical localization of carbamoyl-phosphate synthetase (ammonia) in adult rat liver; evidence for a heterogeneous distribution. , 1984, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[10]  K. Jungermann,et al.  Induction in primary culture of 'gluconeogenic' and 'glycolytic' hepatocytes resembling periportal and perivenous cells. , 2005, European journal of biochemistry.

[11]  K. Jungermann,et al.  Modulation of the glucagon-dependent induction of phosphoenolpyruvate carboxykinase and tyrosine aminotransferase by arterial and venous oxygen concentrations in hepatocyte cultures. , 1981, European journal of biochemistry.

[12]  G. M. Lawrence,et al.  Histochemical and immunohistochemical localization of hexokinase isoenzymes in normal rat liver , 1984, The Histochemical Journal.

[13]  K. Jungermann,et al.  Functional Hepatocellular Heterogeneity , 2007, Hepatology.

[14]  R. W. Jones,et al.  Functional analysis of an oxygen-regulated transcriptional enhancer lying 3' to the mouse erythropoietin gene. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[15]  E. Wisse,et al.  Liver cell heterogeneity: functions of non-parenchymal cells. , 1992, Enzyme.

[16]  M. Jepson,et al.  The compartmentation of glycolytic and gluconeogenic enzymes in rat kidney and liver and its significance to renal and hepatic metabolism , 2005, The Histochemical Journal.

[17]  K. Jungermann,et al.  Nervous control of liver metabolism and hemodynamics. , 1992, European journal of biochemistry.

[18]  K.,et al.  Metabolic effects of developmental, tissue-, and cell-specific expression of a chimeric phosphoenolpyruvate carboxykinase (GTP)/bovine growth hormone gene in transgenic mice. , 1990, The Journal of biological chemistry.

[19]  A. Gressner Liver fibrosis: perspectives in pathobiochemical research and clinical outlook. , 1991, European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies.

[20]  K. Jungermann,et al.  Modulation of the glucagon‐dependent activation of the phosphoenolpyruvate carboxykinase gene by oxygen in rat hepatocyte cultures Evidence for a heme protein as oxygen sensor , 1992, FEBS letters.

[21]  K. Jungermann,et al.  Mechanism of the inhibition by insulin of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures. Action on gene transcription, mRNA level and -stability as well as hysteresis effect. , 1990, Biological chemistry Hoppe-Seyler.

[22]  K. Jungermann,et al.  Heterogeneous reciprocal localization of fructose‐1,6‐bis‐phosphatase and of glucokinase in microdissected periportal and perivenous rat liver tissue , 1977, FEBS letters.

[23]  Gressner Am Liver fibrosis: perspectives in pathobiochemical research and clinical outlook. , 1991 .

[24]  K. Jungermann,et al.  Heterogeneous distribution of phosphoenolpyruvate carboxykinase in rat liver parenchyma, isolated, and cultured hepatocytes. , 1982, European journal of cell biology.

[25]  K. Jungermann,et al.  Predominant periportal expression of the phosphoenolpyruvate carboxykinase and tyrosine aminotransferase genes in rat liver , 1990, Histochemistry.

[26]  F. Welsh CHANGES IN DISTRIBUTION OF ENZYMES WITHIN THE LIVER LOBULE DURING ADAPTIVE INCREASES , 1972, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[27]  K. Jungermann,et al.  A ferro-heme protein senses oxygen levels, which modulate the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures. , 1993, Biochemical and biophysical research communications.

[28]  A. Chiquoine THE DISTRIBUTION OF GLUCOSE-6-PHOSPHATASE IN THE LIVER AND KIDNEY OF THE MOUSE , 1953, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[29]  N. Bass Organization and zonation of hepatic lipid metabolism , 1989 .

[30]  K. Jungermann,et al.  Heterogeneous distribution of glucose‐6‐phosphatase in microdissected periportal and perivenous rat liver tissue , 1977, FEBS letters.

[31]  E. Hertzberg,et al.  Multiple mechanisms are responsible for altered expression of gap junction genes during oncogenesis in rat liver. , 1994, Journal of cell science.

[32]  N. Katz Methods for the study of liver cell heterogeneity , 1989, The Histochemical Journal.

[33]  H. Pitot,et al.  Diurnal variation of the serine dehydratase mRNA level in rat liver. , 1994, Archives of biochemistry and biophysics.

[34]  J. Scoazec,et al.  Functional hepatocellular heterogeneity for the production of plasma proteins. , 1992, Enzyme.

[35]  S. Antonarakis,et al.  Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[36]  D. Sasse Dynamics of liver glycogen , 1975, Histochemistry.

[37]  A. Moorman,et al.  Hepatocyte heterogeneity in the metabolism of amino acids and ammonia. , 1992, Enzyme.

[38]  K. Jungermann,et al.  Predominant localization of phosphoenolpyruvate carboxykinase mRNA in the periportal zone of rat liver parenchyma demonstrated by in situ hybridization , 1989, FEBS letters.

[39]  L. Lumeng,et al.  Intrasplenic transplantation of isolated periportal and perivenous hepatocytes as a long‐term system for study of liver‐specific gene expression , 1994, Hepatology.

[40]  K. Jungermann,et al.  Zonal expression of the glucokinase gene in rat liver. Dynamics during the daily feeding rhythm and starvation-refeeding cycle demonstrated by in situ hybridization , 1993, Histochemistry.

[41]  D. Häussinger,et al.  Hepatocyte heterogeneity in response to icosanoids. The perivenous scavenger cell hypothesis. , 1988, European journal of biochemistry.

[42]  J. Darnell,et al.  Positional and developmental regulation of glutamine synthetase expression in mouse liver , 1988, Molecular and cellular biology.

[43]  K. Jungermann,et al.  Hepatocyte heterogeneity in the metabolism of carbohydrates. , 1992, Enzyme.

[44]  D. Meijer,et al.  Hepatocyte heterogeneity in bile formation and hepatobiliary transport of drugs. , 1992, Enzyme.

[45]  D. Sasse,et al.  The circadian rhythm of intra-acinar profiles of alcohol dehydrogenase activity in rat liver: a microquantitative study , 1990, The Histochemical Journal.

[46]  K. Jungermann,et al.  Glycogen synthesis via the indirect gluconeogenic pathway in the periportal and via the direct glucose utilizing pathway in the perivenous zone of perfused rat liver , 2004, Histochemistry.

[47]  G. Semenza,et al.  Localization of cells producing erythropoietin in murine liver by in situ hybridization. , 1991, Blood.

[48]  R. Thurman,et al.  Biotransformation and Zonal Toxicity , 1986 .

[49]  A. Guillouzo,et al.  Detection of mRNAs present at low concentrations in rat liver by in situ hybridization: application to the study of metabolic regulation and azo dye hepatocarcinogenesis. , 1987, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[50]  W. Fischer,et al.  Reciprocal distribution of hexokinase and glucokinase in the periportal and perivenous zone of the rat liver acinus. , 1982, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[51]  K. Jungermann Zonal liver cell heterogeneity. , 1992, Enzyme.

[52]  K. Jungermann,et al.  Alteration with dietary state of the activity and zonal distribution of adenylate cyclase stimulated by glucagon, fluoride and forskolin in microdissected rat liver tissue. , 1984, European journal of biochemistry.

[53]  W. Guder,et al.  Liver cell heterogeneity. The distribution of pyruvate kinase and phosphoenolpyruvate carboxykinase (GTP) in the liver lobule of fed and starved rats. , 1976, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[54]  J. W. Campbell,et al.  Distribution of glutamine synthetase and carbamoyl-phosphate synthetase I in vertebrate liver. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[55]  D. Häussinger,et al.  Hepatocyte heterogeneity in response to extracellular ATP. , 1987, European journal of biochemistry.

[56]  K. Jungermann,et al.  Functional specialization of different hepatocyte populations. , 1989, Physiological reviews.

[57]  R. Thurman,et al.  SUblobular compartmentation of pharmacologic events (scope): Metabolic fluxes in periportal and pericentral regions of the liver lobule , 1985, Hepatology.

[58]  K. Jungermann,et al.  Predominant periportal expression of the phosphoenolpyruvate carboxykinase gene in liver of fed and fasted mice, hamsters and rats studied by in situ hybridization , 1993, Histochemistry.

[59]  F. Matschinsky,et al.  Hexokinase and glucokinase distribution in the liver lobule. , 1980, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[60]  K. Willecke,et al.  Comparative characterization of the 21-kD and 26-kD gap junction proteins in murine liver and cultured hepatocytes , 1989, The Journal of cell biology.

[61]  B. Quistorff Metabolic heterogeneity of liver parenchymal cells. , 1990, Essays in biochemistry.

[62]  F. Gaunitz,et al.  Heterogeneous (positional) expression of hepatic glutamine synthetase: features, regulation and implications for hepatocarcinogenesis. , 1994, Advances in enzyme regulation.

[63]  R. Gebhardt,et al.  Heterogeneous expression of glutamine synthetase mRNA in rat liver parenchyma revealed by in situ hybridization and Northern blot analysis of RNA from periportal and perivenous hepatocytes , 1988, FEBS letters.

[64]  M. Iwai,et al.  Inhibition of glucose production during hepatic nerve stimulation in regenerating rat liver perfused in situ. Possible involvement of gap junctions in the action of sympathetic nerves. , 1991, European journal of biochemistry.

[65]  P. Traber,et al.  Demonstration by in situ hybridization of the zonal modulation of rat liver cytochrome P-450b and P-450e gene expression after phenobarbital. , 1988, The Journal of clinical investigation.

[66]  M. Harbers,et al.  Zonation of glucokinase in rat liver changes during postnatal development , 1993, FEBS letters.

[67]  A. Moorman,et al.  Complementary distribution of carbamoylphosphate synthetase (ammonia) and glutamine synthetase in rat liver acinus is regulated at a pretranslational level. , 1988, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[68]  S. Thorgeirsson,et al.  Expression of multidrug resistance genes in rat liver during regeneration and after carbon tetrachloride intoxication , 1993, Hepatology.

[69]  K. Jungermann,et al.  Heterogeneity of liver parenchymal cells , 1978 .

[70]  A. Moorman,et al.  Pericentral expression pattern of glucokinase mRNA in the rat liver lobulus , 1991, FEBS letters.

[71]  P. Holst,et al.  Extracellular matrix gradients in the space of disse: Relevance to liver biology , 1992, Hepatology.

[72]  H. Schumacher Histochemical distribution pattern of respiratory enzymes in the liver lobule. , 1957, Science.

[73]  J. McGarry,et al.  The glucose paradox: new perspectives on hepatic carbohydrate metabolism , 1986 .

[74]  K. Jungermann,et al.  Functional heterogeneity of rat liver parenchyma and of isolated hepatocytes , 1975, FEBS letters.

[75]  H. Eisen,et al.  Immunocytochemical localization of glucocorticoid receptor in target cells. , 1984, Endocrinology.

[76]  D. Sasse Liver Structure and Innervation , 1986 .

[77]  M. Oppermann,et al.  Differential effects of human anaphylatoxin C3a on glucose output and flow in rat liver during orthograde and retrograde perfusion: the periportal scavenger cell hypothesis. , 1991, Biochemical and biophysical research communications.

[78]  A. Rappaport Betrachtungen zur Pathophysiologie der Leberstruktur , 1960, Klinische Wochenschrift.

[79]  W H Lamers,et al.  Experimental evidence that the physiological position of the liver within the circulation is not a major determinant of zonation of gene expression , 1993, Hepatology.

[80]  K. Jungermann,et al.  Autoregulatory shift from fructolysis to lactate gluconeogenisis in rat hepatocyte suspensions. The problem of metabolic zonation of liver parenchyma. , 1976, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[81]  R. Gebhardt,et al.  Heterogeneous distribution of glutamine synthetase among rat liver parenchymal cells in situ and in primary culture. , 1983, The EMBO journal.

[82]  K. Jungermann,et al.  Distribution of pyruvate kinase type L and M2 in microdissected periportal and perivenous rat liver tissue with different dietary states. , 1983, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[83]  K. Decker,et al.  Biologically active products of stimulated liver macrophages (Kupffer cells). , 1990, European journal of biochemistry.

[84]  L. Witters,et al.  Hepatocyte heterogeneity in the metabolism of fatty acids: discrepancies on zonation of acetyl-CoA carboxylase. , 1992, Enzyme.

[85]  K. Jungermann,et al.  Modulation by oxygen of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures. , 1991, European journal of biochemistry.

[86]  K. Jungermann,et al.  Signal propagation via gap junctions, a key step in the regulation of liver metabolism by the sympathetic hepatic nerves , 1992, FEBS letters.

[87]  M. Goldberg,et al.  Regulation of the erythropoietin gene: evidence that the oxygen sensor is a heme protein. , 1988, Science.