Home LiteratureArticle Details
PMID: 2687211 Published · ppublish English Journal Article Review

Methods for the study of liver cell heterogeneity.

The Histochemical journal ·Vol. 21 ·No. 9-10 ·1989-00-00 ·Pages 517-29

Katz NR

Abstract

A large number of histological, histochemical and biochemical techniques are available for studying liver cell heterogeneity. Structural differences are recognized by morphometric analyses of electron micrographs. The zonal heterogeneity of enzyme activities can be demonstrated by histochemistry and more precisely by ultramicrobiochemical assays in microdissected periportal and perivenous tissue. Immunohistochemistry is useful for quantifying and localizing proteins, especially isoenzymes, without depending on their biological activity. The zonal quantification of specific mRNA can be achieved by in situ hybridization. The different structural and enzymic equipment of periportal and perivenous tissue found by these techniques has led to the concept of metabolic zonation. This hypothesis can be confirmed by determination of metabolic rates in perfused liver after selective zonal damage, in separated periportal and perivenous hepatocytes as well as in periportal and perivenous tissue of perfused liver by non-invasive techniques.

MeSH Terms
Animals Histocytochemistry/methods Humans Immunohistochemistry/methods Liver/cytology,metabolism,ultrastructure Microscopy, Electron/methods
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Katz N R
Institut für Klinische Chemie und Pathobiochemie, Universitätsklinikum Giessen, Germany.
References (92)
92 references, click to expand
  1. Mechanism of hepatotoxicity in periportal regions of the liver lobule due to allyl alcohol: studies on thiols and energy status.
    J Pharmacol Exp Ther. 1986 Sep;238(3):1132-7 PMID: 3746662
  2. Enzyme-labeled antibodies: preparation and application for the localization of antigens.
    J Histochem Cytochem. 1966 Dec;14(12):929-31 PMID: 17121392
  3. Microphotometric determination of enzyme activity in single cells in cryostat sections. I. Application of the gel film technique to microphotometry and studies on the intralobular distribution of succinate dehydrogenase and lactate dehydrogenase activities in rat liver.
    J Histochem Cytochem. 1972 Aug;20(8):567-76 PMID: 4402953
  4. Stimulation of mixed-function oxidation of 7-ethoxycoumarin in periportal and pericentral regions of the perfused rat liver by xylitol.
    Eur J Biochem. 1983 Dec 1;137(1-2):1-6 PMID: 6606574
  5. NADP-dependent dehydrogenases in rat liver parenchyma. II. Comparison of qualitative and quantitative G6PDH distribution patterns with particular reference to sex differences.
    Histochemistry. 1979 Feb 26;60(1):43-52 PMID: 429212
  6. Measuring rates of O2 uptake in periportal and pericentral regions of liver lobule: stop-flow experiments with perfused liver.
    Am J Physiol. 1983 Jun;244(6):G656-9 PMID: 6859274
  7. Periportal and pericentral pyridine nucleotide fluorescence from the surface of the perfused liver: evaluation of the hypothesis that chronic treatment with ethanol produces pericentral hypoxia.
    Proc Natl Acad Sci U S A. 1982 Sep;79(17 ):5415-9 PMID: 6957871
  8. Heterogeneous reciprocal localization of fructose-1,6-bisphosphatase and of glucokinase in microdissected periportal and perivenous rat liver tissue.
    FEBS Lett. 1977 Nov 15;83(2):272-6 PMID: 201494
  9. Distributions of monooxygenase components and epoxide hydratase within the livers of untreated male rats.
    Life Sci. 1980 Dec 22-29;27(25-26):2465-70 PMID: 6783796
  10. NADP-dependent dehydrogenases in rat liver parenchyma. III. The description of a liponeogenic area on the basis of histochemically demonstrated enzyme activities and the neutral fat content during fasting and refeeding.
    Histochemistry. 1981;72(4):579-615 PMID: 7298391
  11. Microphotometric studies on intraacinar enzyme distribution in rat liver.
    Histochemistry. 1979 Nov;64(1):23-33 PMID: 521313
  12. A quantitative stereological description of the ultrastructure of normal rat liver parenchymal cells.
    J Cell Biol. 1968 Apr;37(1):27-46 PMID: 5645844
  13. Purification of cells from livers of carcinogen-treated rats by free-flow electrophoresis.
    Cancer Res. 1983 Sep;43(9):4176-9 PMID: 6135504
  14. Hepatocyte heterogeneity in glutamine and ammonia metabolism and the role of an intercellular glutamine cycle during ureogenesis in perfused rat liver.
    Eur J Biochem. 1983 Jun 15;133(2):269-75 PMID: 6852039
  15. Periportal and perivenous hepatocytes retain their zonal characteristics in primary culture.
    Biochem Biophys Res Commun. 1986 Sep 30;139(3):1055-61 PMID: 3021146
  16. [The topochemical shift of functional units of glycogen metabolism in the liver by allyl formate].
    Histochemie. 1969;18(4):325-36 PMID: 4187598
  17. A technical note on the histochemical demonstration of G6Pase activity.
    Histochemistry. 1983;78(3):409-11 PMID: 6309705
  18. Quantitation of ketogenesis in periportal and pericentral regions of the liver lobule.
    Arch Biochem Biophys. 1987 Feb 15;253(1):26-37 PMID: 3813565
  19. Nuclear volume and cellular metabolism.
    Adv Anat Embryol Cell Biol. 1980;60:1-54 PMID: 6992523
  20. Functional hepatocellular heterogeneity determined by the hepatotoxins allyl alcohol and bromobenzene in immature and adult Fischer 344 rats.
    Toxicol Appl Pharmacol. 1986 Mar 30;83(1):108-14 PMID: 3006282
  21. Immunohistochemical localization of glutathione S-transferases in livers of untreated rats.
    J Biol Chem. 1982 Dec 25;257(24):15200-3 PMID: 7174691
  22. Dual-digitonin-pulse perfusion. Concurrent sampling of periportal and perivenous cytosol of rat liver for determination of metabolites and enzyme activities.
    Biochem J. 1987 Apr 1;243(1):87-95 PMID: 3606584
  23. The isolation of functionally heterogeneous hepatocytes of the proximal and distal half of the liver acinus in the rat.
    Hepatology. 1986 Sep-Oct;6(5):932-44 PMID: 3019862
  24. Cell size, nuclear content, and the development of polyploidy in the Mammalian liver.
    Proc Natl Acad Sci U S A. 1967 Feb;57(2):327-34 PMID: 16591473
  25. Rates of sulfation and glucuronidation of 7-hydroxycoumarin in periportal and pericentral regions of the liver lobule.
    Mol Pharmacol. 1982 Sep;22(2):509-16 PMID: 7144740
  26. The distribution of albumin synthesis throughout the liver lobule.
    J Cell Biol. 1970 Oct;47(1):285-9 PMID: 5513556
  27. All hepatocytes are involved in the expression of the albumin gene in the normal adult rat: a demonstration by in situ hybridization and immunoperoxidase techniques.
    Cell Biol Int Rep. 1985 Jan;9(1):31-42 PMID: 2579741
  28. Dynamics of liver glycogen: the topochemistry of glycogen synthesis, glycogen content and glycogenolysis under the experimental conditions of glycogen accumulation and depletion.
    Histochemistry. 1975 Dec 8;45(3):237-54 PMID: 814113
  29. Immunohistochemical localizations of cytochromes P-450 in rat liver.
    Life Sci. 1978 Dec 25;23(26):2627-32 PMID: 739843
  30. Hepatocyte heterogeneity in ammonia metabolism: impairment of glutamine synthesis in CCl4 induced liver cell necrosis with no effect on urea synthesis.
    Chem Biol Interact. 1984 Feb;48(2):191-4 PMID: 6697421
  31. Quantitative analysis of regenerating and degenerating areas within the lobule of the carbon tetrachloride-injured liver.
    Arch Biochem Biophys. 1965 Aug;111(2):448-60 PMID: 5862004
  32. Reciprocal distribution of hexokinase and glucokinase in the periportal and perivenous zone of the rat liver acinus.
    Hoppe Seylers Z Physiol Chem. 1982 Apr;363(4):375-80 PMID: 7076132
  33. Immunohistochemical study of epoxide hydrolase during experimental liver carcinogenesis.
    Cancer Res. 1981 Sep;41(9 Pt 1):3281-7 PMID: 7020925
  34. Cytochemical demonstration of ornithine carbamoyltransferase activity in liver mitochondria of rat and mouse.
    J Histochem Cytochem. 1968 Mar;16(3):172-80 PMID: 4172322
  35. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study.
    J Cell Biol. 1969 Dec;43(3):506-20 PMID: 4900611
  36. Autoradiographic and kinetic demonstration of acinar heterogeneity of taurocholate transport.
    Am J Physiol. 1982 Dec;243(6):G455-62 PMID: 7149029
  37. A random arrangement of albumin-containing hepatocytes seen with histo-immunologic methods. II. Conditions that produce the artifact.
    Anat Rec. 1980 Jun;197(2):195-201 PMID: 6998324
  38. Heterogeneous distribution of ATP citrate lyase in rat-liver parenchyma. Microradiochemical determination in microdissected periportal and perivenous liver tissue.
    Eur J Biochem. 1983 Feb 1;130(2):297-301 PMID: 6825695
  39. Selective isolation of intact periportal or perivenous hepatocytes by antero- or retrograde collagenase gradient perfusion.
    Liver. 1983 Jun;3(3):131-9 PMID: 6312242
  40. Principle and method of kinetic microphotometric enzyme activity determination in situ.
    Histochemistry. 1979 Nov;64(1):1-10 PMID: 521310
  41. Digitonin perfusion of rat liver. A new approach in the study of intra-acinar and intracellular compartmentation in the liver.
    Biochem J. 1985 Feb 15;226(1):289-97 PMID: 3977871
  42. Hexokinase and glucokinase distribution in the liver lobule.
    J Histochem Cytochem. 1980 Jun;28(6):579-81 PMID: 7391551
  43. Bifunctional reagents as vapour- and liquid-phase fixatives for immunohistochemistry.
    Histochem J. 1975 Mar;7(2):179-86 PMID: 1092636
  44. Heterogeneous distribution of glutamine synthetase among rat liver parenchymal cells in situ and in primary culture.
    EMBO J. 1983;2(4):567-70 PMID: 6138251
  45. An immunohistochemical study on the localization and distributions of phenobarbital- and 3-methylcholanthrene-inducible cytochromes P-450 within the livers of untreated rats.
    J Biol Chem. 1981 Jun 10;256(11):5931-7 PMID: 7016864
  46. Retrograde perfusion to probe the heterogeneous distribution of hepatic drug metabolizing enzymes in rats.
    J Pharmacol Exp Ther. 1981 Feb;216(2):339-46 PMID: 7463352
  47. Scanning microdensitometry of glycogen zonation in the livers of rats adapted to a controlled feeding schedule and to 30, 60, or 90% casein diets.
    Am J Anat. 1980 Jan;157(1):71-85 PMID: 7190772
  48. A quantitative description of cortisone-induced alterations in the ultrastructure of rat liver parenchmal cells.
    J Cell Biol. 1968 Apr;37(1):47-61 PMID: 5645845
  49. A random arrangement of albumin-containing hepatocytes seen with histo-immunologic methods. I. Verification of the artifact.
    Anat Rec. 1980 Jun;197(2):183-94 PMID: 6998323
  50. Separation of intact rat hepatocytes and rat liver nuclei into ploidy classes by velocity sedimentation at unit gravity.
    Biochim Biophys Acta. 1976 Dec 21;451(2):567-82 PMID: 999869
  51. Partial separation and biochemical characteristics of periportal and perivenous hepatocytes from rat liver.
    Eur J Biochem. 1981 Sep 1;118(3):591-7 PMID: 7028482
  52. Isolation and subfractionation on ficoll gradients of adult rat hepatocytes. Size, morphology, and biochemical characteristics of cell fractions.
    J Cell Biol. 1975 Jul;66(1):1-22 PMID: 167028
  53. Facilitation of microdissection by use of a new microscopic and micromanipulatory unit.
    Naturwissenschaften. 1982 Mar;69(3):146-7 PMID: 6281661
  54. Effects of 3-methylcholanthrene, beta-naphthoflavone, and phenobarbital on the 3-methylcholanthrene-inducible isozyme of cytochrome P-450 within centrilobular, midzonal, and periportal hepatocytes.
    J Biol Chem. 1982 Jan 25;257(2):953-7 PMID: 7054190
  55. A non-invasive method to study metabolic events within sublobular regions of hemoglobin-free perfused liver.
    FEBS Lett. 1980 Apr 21;113(1):37-42 PMID: 7380004
  56. The microcirculatory acinar concept of normal and pathological hepatic structure.
    Beitr Pathol. 1976 May;157(3):215-43 PMID: 1275864
  57. [Separation of metabolically distinct cell fractions from isolated rat hepatocytes].
    Exp Cell Res. 1969 Oct;57(2):211-22 PMID: 4390634
  58. Microquantitative determination of the distribution patterns of alcohol dehydrogenase activity in the liver of rat, guinea-pig and horse.
    Histochemistry. 1985;83(5):431-6 PMID: 2934353
  59. Distribution of enzymes of fatty acid and ketone body metabolism in periportal and perivenous rat-liver tissue.
    Eur J Biochem. 1983 Sep 1;135(1):103-7 PMID: 6136405
  60. Histochemical and immunohistochemical localization of hexokinase isoenzymes in normal rat liver.
    Histochem J. 1984 Oct;16(10):1099-111 PMID: 6094398
  61. Autoradiographic evidence for hepatic lobular concentration gradient of bile acid derivative.
    Am J Physiol. 1980 Mar;238(3):G233-7 PMID: 7369371
  62. Gluconeogenesis predominates in periportal regions of the liver lobule.
    Eur J Biochem. 1984 Nov 2;144(3):409-15 PMID: 6489336
  63. Biochemical changes after hepatic injury by allyl alcohol and N-hydroxy-2-acetylaminofluorene.
    Chem Biol Interact. 1976 Oct 2;15(2):139-47 PMID: 184970
  64. Hepatotoxicity due to allyl alcohol in deermice depends on alcohol dehydrogenase.
    Hepatology. 1985 Nov-Dec;5(6):1179-82 PMID: 2933316
  65. Development of ultrastructural heterogeneity among hepatocytes in the mouse.
    Anat Rec. 1982 Mar;202(3):395-405 PMID: 7072985
  66. Heterogeneous distribution of glucose-6-phosphatase in microdissected periportal and perivenous rat liver tissue.
    FEBS Lett. 1977 Apr 15;76(2):226-30 PMID: 193728
  67. Distribution of pyruvate kinase type L and M2 in microdissected periportal and perivenous rat liver tissue with different dietary states.
    Hoppe Seylers Z Physiol Chem. 1983 Oct;364(10):1447-53 PMID: 6642430
  68. Immunohistochemical localization of epoxide hydratase in rat liver.
    Life Sci. 1980 Feb 11;26(6):489-93 PMID: 6990148
  69. Heterogeneity of protein metabolism between liver cells as studied by radioautography.
    Curr Mod Biol. 1968 May-Jun;2(2):111-4 PMID: 5649998
  70. Isolation of rat liver cells containing concanavalin-A receptor sites.
    FEBS Lett. 1974 Oct 1;47(1):11-4 PMID: 4372083
  71. Predominance of glycolysis in pericentral regions of the liver lobule.
    Eur J Biochem. 1984 Apr 16;140(2):229-34 PMID: 6714231
  72. Gluconeogenesis in periportal and perivenous hepatocytes of rat liver, isolated by a new high-yield digitonin/collagenase perfusion technique.
    Biochem J. 1985 Jul 1;229(1):221-6 PMID: 2994630
  73. Immunohistochemical localization of carbamoyl-phosphate synthetase (ammonia) in adult rat liver; evidence for a heterogeneous distribution.
    J Histochem Cytochem. 1984 Jun;32(6):557-64 PMID: 6373912
  74. A morphometric study of the variations in subcellular structures of rat hepatocytes during 24 hours.
    Cell Tissue Res. 1984;236(2):305-15 PMID: 6733756
  75. Micro-light guides: a new method for measuring tissue fluorescence and reflectance.
    Am J Physiol. 1979 Mar;236(3):C144-56 PMID: 426046
  76. On the nature of protein benzoquinone complexes.
    Experientia. 1976 Dec 15;32(12):1502-3 PMID: 1021431
  77. Greater taurodeoxycholate biotransformation during backward perfusion of rat liver.
    Am J Physiol. 1986 Oct;251(4 Pt 1):G431-5 PMID: 3766730
  78. The measurement of pyridine nucleotides by enzymatic cycling.
    J Biol Chem. 1961 Oct;236:2746-55 PMID: 14466981
  79. The differential localization of various drug metabolizing systems within the rat liver lobule as determined by the hepatotoxins allyl alcohol, carbon tetrachloride and bromobenzene.
    J Pharmacol Exp Ther. 1981 Apr;217(1):127-32 PMID: 7205647
  80. Chemomorphology of liver parenchyma. Qualitative histochemical distribution patterns and quantitative sinusoidal profiles of G6Pase, G6PDH and malic enzyme activity and of glycogen content.
    Prog Histochem Cytochem. 1981;14(3):1-92 PMID: 6283597
  81. Experimental alcohol-induced hepatic necrosis: suppression by propylthiouracil.
    Proc Natl Acad Sci U S A. 1975 Mar;72 (3):1137-41 PMID: 1055371
  82. Continous monitoring of ATP-converting reactions by purified firefly luciferase.
    Anal Biochem. 1976 Oct;75(2):611-20 PMID: 10755
  83. Peri- and postnatal development of heterogeneity in the amounts of endoplasmic reticulum in mouse hepatocytes.
    Am J Anat. 1986 Apr;175(4):471-80 PMID: 3717049
  84. Normal and retrograde perfusion to probe the zonal distribution of sulfation and glucuronidation activities of harmol in the perfused rat liver preparation.
    J Pharmacol Exp Ther. 1983 Mar;224(3):647-53 PMID: 6827487
  85. Heterogeneous distribution of phosphoenolpyruvate carboxykinase in rat liver parenchyma, isolated, and cultured hepatocytes.
    Eur J Cell Biol. 1982 Aug;28(1):47-53 PMID: 6751828
  86. Drug metabolism as a cause of drug toxicity.
    Drug Metab Dispos. 1973 Jan-Feb;1(1):418-23 PMID: 4149413
  87. Liver cell heterogeneity. The distribution of pyruvate kinase and phosphoenolpyruvate carboxykinase (GTP) in the liver lobule of fed and starved rats.
    Hoppe Seylers Z Physiol Chem. 1976 Dec;357(12):1793-800 PMID: 1017801
  88. The compartmentation of glycolytic and gluconeogenic enzymes in rat kidney and liver and its significance to renal and hepatic metabolism.
    Histochem J. 1986 Jan;18(1):45-53 PMID: 2423478
  89. A quantitative histochemical study of NADPH-ferrihemoprotein reductase activity.
    Histochem J. 1986 Jul;18(7):364-70 PMID: 3093410
  90. High spatial resolution readout of 3-D metabolic organ structure: an automated, low-temperature redox ratio-scanning instrument.
    Anal Biochem. 1985 Aug 1;148(2):389-400 PMID: 4061818
  91. Zonal redox changes as a cause of selective perivenular hepatotoxicity of alcohol.
    Pharmacol Biochem Behav. 1983;18 Suppl 1:449-54 PMID: 6685304
  92. Carbon tetrachloride hepatotoxicity: an example of lethal cleavage.
    CRC Crit Rev Toxicol. 1973 Nov;2(3):263-97 PMID: 4357489
Article Info
Journal
The Histochemical journal
Abbr.
Histochem J
ISSN
0018-2214
Published
1989-00-00
Pages
517-29
Language
English
Region
Netherlands
NLM ID
0163161
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com