A New Function for an Old Enzyme: The Role of DNase I in Apoptosis

  • H. G. Mannherz
  • M. C. Peitsch
  • S. Zanotti
  • R. Paddenberg
  • B. Polzar
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 198)

Abstract

Programmed cell death or apoptosis (Greek for the falling of the leafs in autumn) is an event by which cells are deliberately eliminated (recently reviewed by Ucker 1991, Williams et al. 1992 and Cohen 1993). It occurs during embryogenesis, during the formation of digits from a limb bud, during the selection of immunocompetent B or autoreactive T cells, and in many tissues to provide a stable balance of cellular mass. The morphologic events during apoptosis differ from those of necrosis, defined as the dying of cells by plasma membrane injury. During apoptosis, the nuclear chromatin rapidly condenses to form crescent-shaped deposits along the nuclear envelope. The nucleus convolutes and fragments, while the cytoplasmic membrane forms protuberances. These are subsequently released forming so-called apoptotic bodies containing highly condensed DNA. The whole cell may disintegrate into a large number of membrane-sealed apoptotic bodies which are immediately phagocytosed by neighboring cells or macrophages. Apoptosis affects only single cells dispersed in a given tissue and there is no release of cytoplasmic contents into the extracellular space and therefore no inflammatory reaction is induced. In contrast, necrotic cell death usually affects a large number of neighboring cells. Due to the membrane injury, cytoplasmic contents leak into the extracellular space and an inflammatory reaction ensues.

Keywords

Hydrolysis Estrogen Leukemia Testosterone Luminal 

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References

  1. Bacher M, Rausch U, Goebel HW, Polzar B, Mannherz HG, Aumuller G (1993) Stromal and epirthelial cells from rat ventral prostate during androgen deprivation and estrogen treatment-regulation of transcription. Exp Clin Endocrinol 101: 78–86PubMedCrossRefGoogle Scholar
  2. Blikstad I, Markey F, Carlsson L, Persson T, Lindberg U (1978) Selective assay of monomeric and filamentous actin in cell extracts, using inhibition of deoxyribonuclease 1, Cell 15: 935–943PubMedCrossRefGoogle Scholar
  3. Booth C, Koch GL (1989) Perturbation of cellular calcium induces secretion of luminal ER proteins. Cell 59: 729–737PubMedCrossRefGoogle Scholar
  4. Campbell WW, Jackson DA (1980) The effect of divalent cations on the mode of action of DNase I. The initial reaction products produced from covalently closed circular DNA. J Biol Chem 255: 3726–3735Google Scholar
  5. Chitrabamrung S, Rubin RL, Tan EM (1981) Serum deoxyribonuclease I and clinical activity in systematic lupus erythematosus. Rheumatol. Int 1: 55–60Google Scholar
  6. Cohen JJ (1993) Apoptosis. Immunol Today 14: 126–130Google Scholar
  7. Cooper EJ, Trautmann ML, Laskowski M (1950) Occurrence and distribution of an inhibitor for deoxyribonuclease in animal tissues. Proc Soc Biol Med 73: 219–222Google Scholar
  8. Drabowska W, Cooper EJ, Laskowski M (1949) A specific inhibitor for deoxyribonuclease J Biol Chem 177: 991–992Google Scholar
  9. Festy B, Paoletti C (1963) Measurement of neutral deoxyribonuclease activity (by liberation of soluble oligonucleotides). Compt Rend H Acad Sei 257: 3682–3685Google Scholar
  10. Fukui Y, Katsumaru H (1979) Nuclear actin bundles in Amoeba Dictyostelium and human HeLa cells induced by dimethyl sulforide. Exp Cell Res 120: 451–455PubMedCrossRefGoogle Scholar
  11. Gavrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labelling of nuclear DNA fragmentation J Cell Biol 119: 493–501Google Scholar
  12. Hewish DR, Burgoyne LA (1973) Chromatin sub-structure. The digestion of chromatin DNA at regularly spaced sites by a nuclear deoxyribonuclease. Biochem Biophys Res Commun 52: 504–510Google Scholar
  13. Hitchcock SE, Carlsson L, Lindberg U (1976) Depolymerization of F-actin by deoxyribonuclease I. Cell 7: 531–542PubMedCrossRefGoogle Scholar
  14. Kabsch W, Mannherz HG, Suck D, Pai EF, Holmes KC (1990) Atomic structure of actin: DNase I complex. Nature 347: 37–44Google Scholar
  15. Kishi K, Yasuda T, Ikehara Y, Sawazaki K, Sato W, Lida R (1990) Human serum deoxyribonuclease I (DNase I) polymorphism: pattern similarities among isoenzymes from serum, urine, kidney, liver, and pancreas. Am J Hum Genet 47: 121–126PubMedGoogle Scholar
  16. Kolber MA, Broschat KO, Landa-Gonzalez B (1990) Cytochalasin B induces cellular DNA fragmentation. FASEBJ 4: 3021–3027Google Scholar
  17. Kossel A (1894) Weitere Beiträge zur Kenntnis der Nucleinsauren. Arch Anat Physiol 195: 1–2Google Scholar
  18. Kreuder V, Dieckhoff J, Sittig M, Mannherz HG (1984) Isolation, characterization and crystallisation of deoxyribonuclease I from bovine and rat parotid gland and its interaction with rabbit skeletal muscle actin. Eur J Biochem 139: 389–400PubMedCrossRefGoogle Scholar
  19. Kunitz M (1940) Crystalline ribonuclease. J Gen Physiol 24: 15PubMedCrossRefGoogle Scholar
  20. Kunitz M (1948) Isolation of crystalline deoxyribonuclease from beef pancreas. Science 108: 19–20PubMedCrossRefGoogle Scholar
  21. Kunitz M (1950) Crystalline deoxyribonuclease I. Isolation and general properties. J Gen Physiol 33: 349–362PubMedCrossRefGoogle Scholar
  22. Lacks SA (1981) Deoxyribonuclease I in mammalian tissues. Specificity of inhibition by actin. J Biol Chem 256: 2644–2648PubMedGoogle Scholar
  23. Lahm A, Suck D (1991) DNase I induced DNA conformation. 2 Ä structure of a DNase l-octamer complex. J Mol Biol 222: 645–667PubMedCrossRefGoogle Scholar
  24. Lazarides E, Lindberg U (1974) Actin is the naturally occurring inhibor of deoxyribonuclease I. Proc Natl Acad Sei USA 71: 4742–4746CrossRefGoogle Scholar
  25. Liao TH, Salnikow J, Moore S, Stein WH (1973) Bovine pancreatic deoxyribonuclease A. Isolation of cynogen bromide peptides; complete covalent structure of the polypeptide chain, J Biol Chem 248: 1489–1495Google Scholar
  26. Lindberg U (1964) Purification of an inhibitor of pancreatic deoxyribonuclease from calf spleen. Biochim Biophys Acta 82: 237–248CrossRefGoogle Scholar
  27. Lindberg U (1967) Studies on the complex formation between deoxyribonuclease I and spleen inhibitor II. Biochemistry 6: 343–347PubMedCrossRefGoogle Scholar
  28. Lommosoff GP, Butler PJG and Klug A (1981) Sequence-dependent variation in the conformation of DNA. J Mol Biol 149: 745–760CrossRefGoogle Scholar
  29. Maliska Blaszkiewicz, M, Roth JS (1983) Evidence for the presence of DNase- actin complex in L1210 leukemia cells. FEBS Lett 153: 235–239CrossRefGoogle Scholar
  30. Maliska Blaszkiewicz M (1986) DNase l-like activity and actin content in the liver of some vertebrates. Comp Biochem Physiol 84: 207–209Google Scholar
  31. Maliska Blaszkiewicz M (1990) Rat liver DNase l-like activity and its interaction with actin. Z Naturforsch (C) 45: 1165–1170Google Scholar
  32. Mannherz HG, Barrington Leigh J, Leberman R, Pfrang H. (1975) A specific 1:1 G-actin: DNAase I complex formed by the action of DNAase I on F-actin. FEBS Lett 60: 34–38Google Scholar
  33. Mannherz HG, Kabsch W, Leberman R (1977) Crystals of skeletal muscle actin; pancreatic DNAase I complex. FEBS Lett 73: 141–143PubMedCrossRefGoogle Scholar
  34. Mannherz HG, Goody RS, Konrad M, Nowak E (1980) The interaction of bovine pancreatic deoxyribonuclease I and skeletal muscle actin. Eur J Biochem 104: 367–379PubMedCrossRefGoogle Scholar
  35. McConkey DJ, Nicotera P, Hartzell P, Bellomo G, Wyllie AH, Orrenius S (1989) Glucocorticoids activate a suicide process in thymocytes through elevation of cytosolic Ca2+- concentration. Arch Biochem Biophys 269: 365–370PubMedCrossRefGoogle Scholar
  36. Nakayasu H, Ueda K (1983) Association of actin with nuclear matrix from bovine lymphocytes. Exp Cell Res. 143: 55–62PubMedCrossRefGoogle Scholar
  37. Oberhammer FA, Pavelka M, Sharma S, Tiefenbacher R, Purchino AF, Bursch W, Schulte-Hermann R (1992) Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor ß 1. Proc Natl Acad Sei USA 89: 5408–5412CrossRefGoogle Scholar
  38. Oefner C, Suck D (1986) Crystallographic refinement and structure of DNase I at 2 Ä resolution. J Mol Biol 192: 605–632PubMedCrossRefGoogle Scholar
  39. Paddenberg R, Hüttemann B, Wulf S, Mannherz HG (1994) Endonuclease activities of the human pancreatic tumor cell line PaTu 8902LM during cycloheximide induced apoptosis. Eur J Cell Biol 63 [Suppl. 40]: 30Google Scholar
  40. Peitsch MC, Hesterkamp T, Polzar B, Mannherz HG, Tschopp J (1992) Functional characterization of serum DNase I in MRL-lpr/lpr mice. Biochem Biophys Res Commun 186: 739–745PubMedCrossRefGoogle Scholar
  41. Peitsch MC, Polzar B, Stephan H, Crompton T, MacDonald HR, Mannherz HG, Tschopp J (1993a) Characterization of the endogenous deoxyribonuclease involved in nuclear DNA degradation during apoptosis (programmed cell death). EMBO J 12: 371–377PubMedGoogle Scholar
  42. Peitsch MC, Müller C and Tschopp (1993b) DNA fragmentation during apoptosis is caused by frequent single strand cuts. Nucl Acids Res 18: 4206–4209CrossRefGoogle Scholar
  43. Peitsch MC, Mannherz HG, Tschopp J (1994) The apoptosis endonucleases: Cleaning up after cell death. Trends Cell Biol 4: 37–41Google Scholar
  44. Price PA, Stein WH, Moore S (1969) Effect of divalent cations on the reduction and re-formation of the disulfide bonds of deoxyribonuclease, J Biol Chem 244: 929–932PubMedGoogle Scholar
  45. Price PA, Liu TY, Stein WH, Moore S (1969) Properties of chromatographically purified bovine pancreative deoxyribonuclease, J Biol Chem 244: 917–923PubMedGoogle Scholar
  46. Polzar B, Mannherz HG (1990) Nucleotide sequence of a full length cDNA clone encoding the deoxyribonuclease I from the rat parotid gland. Nucleic Acids Res 18: 7151PubMedCrossRefGoogle Scholar
  47. Polzar B, Peitsch MC, Loos R, Tschopp J, Mannherz HG (1993) Overexpression of deoxyribonuclease I ( DNase I) transfected into COS-cells; its distribution during apoptotic death. Eur J Cell Biol 62: 397–405Google Scholar
  48. Polzar B, Zanotti S, Stephan H, Rauch F, Peitsch MC, Irmler M, Tschopp J, Mannherz HG (1994) Distribution of deoxyribonuclease I in rat tissues and its correlation to cellular turnover and apoptosis (programmed cell death). Eur J Cell Biol 64: 200–210PubMedGoogle Scholar
  49. Rohr G, Mannherz HG (1978) Isolation and characterization of secretory actin: DNase I complex from rat pancreatic juice. Eur J Biochem 89: 151–157Google Scholar
  50. Suck D (1982) Crystallisation and preliminary crystallographic data of bovine pancreatic deoxyribonuclease I. J Mol Biol 162: 511–513PubMedCrossRefGoogle Scholar
  51. Suck D, Oefner C, Kabsch W (1984) Three-dimensional structure of bovine pancreatic DNase I at 2.5 Å resolution, EMBO J 3: 2423–2430PubMedGoogle Scholar
  52. Suck D, Oefner C (1986) Structure of DNase I at 2.0 Ä resolution suggests a mechanism for binding to and cutting DNA. Nature 321: 620–625PubMedCrossRefGoogle Scholar
  53. Suck D, Lahm A, Oefner C (1988) Structure refined to 2 Ä of a nicked DNA octanucleotide complex with DNase I. Nature 332: 464–468PubMedCrossRefGoogle Scholar
  54. Ucker DS (1991) Death by suicide: One way to go in mammalian cellular development? New Biol 3: 103–109PubMedGoogle Scholar
  55. Ucker DS, Obermiller PS, Eckhart W, Apgar JR, Berger NA, Meyers J (1992) Genome digestion is a dispensable consequence of physiological cell death mediated by cytotoxic T lymphocytes. Mol Cell Biol 12: 3060–3069PubMedGoogle Scholar
  56. Valkov NI, Ivanova MI, Uscheva AA, Krachmarov CP (1989) Association of actin with DNA and nuclear matrix from Guerin ascites tumor cells. Mol Cell Biochem 87: 47–56PubMedCrossRefGoogle Scholar
  57. Williams GT, Smith CA, McCarthy NJ, Grimes EA (1992) Apoptosis: Final control point in cell biology. Trends Cell Biol 2: 263–267Google Scholar
  58. Wyllie AH (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284: 555–556PubMedCrossRefGoogle Scholar
  59. Zanotti S, Polzar B, Doll K, Stephan H, Niessing J, Mannherz HG (1995) Localization of deoxyribonuclease I gene transcripts in rat tissues and its correlation to apoptotic cell elimination. Histochem (in press)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • H. G. Mannherz
    • 1
    • 3
  • M. C. Peitsch
    • 2
  • S. Zanotti
    • 1
  • R. Paddenberg
    • 1
  • B. Polzar
    • 1
  1. 1.Institute of Cytobiology and CytopathologyMarburgGermany
  2. 2.Glaxo Institute of Molecular BiologyPlan-Les-OuatesSwitzerland
  3. 3.Institute of Anatomy and EmbryologyRuhr-UniversitätBochumGermany

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