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Regulation and Mechanisms of Apoptosis in T Lymphocytes

  • Conference paper

Part of the Archives of Toxicology book series (TOXICOLOGY,volume 19)

Abstract

Apoptotic cell death is now widely recognised as being a distinct process of importance in both normal physiology and pathology. It is characterised by morphological and biochemical changes in most cell compartments (Kerr et al., 1972; Wyllie et al., 1980). The microscopically observed nuclear alterations such as marginatiom and condensation of chromatin and nuclear fragmentation are accompanied by sequential degradation of the DNA, first into fragments of approximately 700, 300 and 50 kilobasepairs and then into small oligonucleosomal fragments which are multiples of about 200 basepairs. This multi-step process can be readily visualised by appropriate electrophoresis of DNA (Walker et al., 1995). Most cell types also show a remarkable shrinkage presumably due to the loss of water and electrolytes and the cytoplasm gradually becomes more electron dense. The plasma membrane remains remarkably intact, though it blebs and the phospholipids redistribute. The specific translocation of phosphatidylserine to the outer leaflet of the plasma membrane has been shown to play a very important role in the recognition of apoptotic cells by phagocytes (Martin et al., 1995). In addition, other membrane changes have been reported to contribute in the specific recognition and removal of the apoptotic bodies that remain after fragmentation of the dead cell (Savill et al., 1993). In this final stage of the process, the dying cells do usually not spill their contents into the extracellular space and consequently the potential for inflammation is limited.

Keywords

  • Apoptotic Cell Death
  • Cell Death Diff
  • Pyrrolidine Dithiocarbamate
  • Short Term Incubation
  • Thymocyte Apoptosis

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  • Ameisen JC, Estaquier J, Idziorek T and De Bels F (1995) Programmed cell death and AIDS: significance, perspectives and unanswered questions. Cell Death Diff 2: 9–22.

    CAS  Google Scholar 

  • Ashkenas J and Werb Z (1996) Proteolysis and the biochemistry of life or death decisions. J Exp Med 183:1947–1951.

    PubMed  CrossRef  CAS  Google Scholar 

  • Beaver JP and Waring P (1995) A decrease in intracellular glutathione concentration precedes the onset of apoptosis in murine thymocytes. Eur J Cell Biol 68: 47–54.

    PubMed  CAS  Google Scholar 

  • Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A and Duke RC (1995) A role for CD95 ligand in preventing graft rejection. Nature 377: 630–632.

    PubMed  CrossRef  CAS  Google Scholar 

  • Bessho R., Matsubara K, Kubota M, Kuwakado K, Hirota H, Wakazono Y, Lin YW, Okuda A., Kawai M, Nishikomori R and Heike T (1994) Pyrrolidine dithiocarbamate, a potent inhibitor of NFKB activation, prevents apoptosis in human promyelocyte leukemia HL-60 cells and thymocytes. Bioch Pharmacol 48:1883–1889.

    CrossRef  CAS  Google Scholar 

  • Boldin MP, Goncharov TM, Goitsev YV and Wallach D (1996) Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 85: 803–815.

    PubMed  CrossRef  CAS  Google Scholar 

  • Briehl MM, Cotgreave IA and Powis G (1995) Downregulation of the antioxidant defense during glucocorticoid-mediated apoptosis. Cell Death Diff 2: 41–46.

    CAS  Google Scholar 

  • Brunner T, Mogil RJ, LaFace D, Yoo NJ, Mahboubi A, Echeverri, Martin SJ, Force WR, Lynch DH, Ware CF and Green DR (1995) Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis I T-cell hybridomas. Nature 373: 441–444.

    PubMed  CrossRef  CAS  Google Scholar 

  • Bustamante J, Slater AFG and Orrenius S (1995) Antioxidant inhibition of thymocyte apoptosis by dihydrolipoic acid. Free Rad Biol Med 19:339–347.

    PubMed  CrossRef  CAS  Google Scholar 

  • Casciola-Rosen L, Nicholson DW, Chong T, Rowan KR, Thornberry N, Miller DK and Rosen A (1996) Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic cell death. J Exp Med 183: 1957–1964.

    PubMed  CrossRef  CAS  Google Scholar 

  • Dhein J, Walczak H, Bäumler C, Debatin KM and Krammer PH (1995) Autocrine T cell suicide mediated by APO-1/(Fas/CD95). Nature 373: 438–441.

    PubMed  CrossRef  CAS  Google Scholar 

  • Dypbukt JM, Ankarcrona M, Burkitt M, Sjöholm Å, Ström K, Orrenius S and Nicotera P (1994) Different prooxidant levels stimulate cell growth, activate apoptosis, or produce necrosis in insulin-secreting RINm5F cells. J Biol Chem 269: 30553–30560.

    PubMed  CAS  Google Scholar 

  • Gougeon ML (1995) Does apoptosis contribute to CD4 T cell depletion in human immunodeficiency virus infection? Cell Death Diff 2: 1–8.

    CAS  Google Scholar 

  • Greenlund LJS, Deckwerth TL and Johnson EM, Jr. (1995) Superoxide dismutase delays neuronal apoptosis: A role for reactive oxygen species in programmed neuronal death. Neuron, 14: 303–314.

    PubMed  CrossRef  CAS  Google Scholar 

  • Griffith TS, Brunner T, Fletcher SM, Green DR and Ferguson TA (1995) Fas ligand- induced apoptosis as a mechanism of immuneprivilege. Nature 370: 1189–1192.

    Google Scholar 

  • Jacobson MD and Raff MC (1995) Programmed cell death and Bcl-2 protection in very low oxygen. Nature 374: 814–816.

    PubMed  CrossRef  CAS  Google Scholar 

  • Jacobson MD (1996) Reactive oxygen species and programmed cell death. Trends in Bioch Sci 21: 83–86.

    CAS  Google Scholar 

  • Kerr JFR, Wyllie AH and Currie AR (1972) Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer 26: 239–257.

    PubMed  CrossRef  CAS  Google Scholar 

  • Lennon SV, Martin SJ and Cotter TG (1991) Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli. Cell Proliferation 24: 203–204.

    PubMed  CrossRef  CAS  Google Scholar 

  • Martin SJ and Green DR (1995) Protease activation during apoptosis: death by a thousand cuts? Cell 82: 349–352.

    PubMed  CrossRef  CAS  Google Scholar 

  • Martin SJ, O’Brien GA, Nishioka WK, McGahon AJ, Mahoubi A, Saido and Green DR (1995) Proteolysis of fodrin (non-erythroid spectrin) during apoptosis. J Biol Chem 270: 6425–6428.

    PubMed  CrossRef  CAS  Google Scholar 

  • Martin SJ, Reutelingsberger CPM, McGahon AJ, Rader JA, Van Schie RCAA, LaFace DM and Green DR (1995) Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med 182: 1545–1556.

    PubMed  CrossRef  CAS  Google Scholar 

  • McConkey DJ, Zhivotovsky B and Orrenius S (1996) Apoptosis - Molecular mechanisms and biomedical implications. Mol Asp Med 17: 1–110.

    CrossRef  CAS  Google Scholar 

  • Muschel RJ, Bernhard EJ, Garza L, McKenna WG and Koch C (1995) Induction of apoptosis at different oxygen tensions: Evidence that oxygen radicals do not mediate apoptotic signaling. Cancer Res 55: 995–998.

    PubMed  CAS  Google Scholar 

  • Muzio M, Chinnaiyan AM, Kischkel FC, O’Rourke K, Shevchenko A, Ni J, Scafidi K, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter M and Dixit VM (1996) FLICE, a novel F ADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) Death Inducing Signaling Complex. Cell 85: 817–827.

    PubMed  CrossRef  CAS  Google Scholar 

  • Nagata S and Golstein P (1995) The Fas death factor. Nature 267: 1449–1455.

    CAS  Google Scholar 

  • Nobel CSI, Kimland M, Lind B, Orrenius S and Slater AFG (1995) Dithiocarbamates induce apoptosis in thymocytes by raising the intracellular level of redox-active copper. J Biol Chem 270: 26202–26208.

    PubMed  CrossRef  CAS  Google Scholar 

  • Savill JS, Fadok V, Henson P and Haslett C (1993) Phagocyte recognition of cells undergoing apoptosis. Immunol Today 14: 131–136.

    PubMed  CrossRef  CAS  Google Scholar 

  • Schlegel J, Peters I, Orrenius S, Miller DK, Thornberry NA, Yamin TT and Nicholson DW (1996) CPP32 is the ICE-like protease in Fas-mediated apoptosis. J Biol Chem 271: 1841–1844.

    PubMed  CrossRef  CAS  Google Scholar 

  • Shimizu S, Eguchi Y, Kosaka H, Kamiike W, Matsuda H and Tsujimoto Y (1995) Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL. Nature 374: 811–813.

    PubMed  CrossRef  CAS  Google Scholar 

  • Slater AFG, Nobel CSI, Maellaro E, Bustamante J, Kimland M and Orrenius S (1995) Nitrone spin traps and a nitroxide antioxidant inhibit a common pathway of thymocyte apoptosis. Biochem J 306: 771–778.

    PubMed  CAS  Google Scholar 

  • Torres-Roca JF, Le Coeur H, Amatore C and Gougeon ML (1995) The early intracellular production of reactive oxygen species mediates apoptosis in dexamethasone-treated thymocytes. Cell Death Diff 2: 309–319.

    CAS  Google Scholar 

  • Van den Dobbelsteen DJ, Nobel CSI, Schlegel J, Cotgreave IA, Orrenius S and Slater AFG (1996a) Rapid and specific efflux of reduced glutathione during apoptosis induced by anti-Fas/APO-1 antibody. J Biol Chem 271: 15420–15427.

    PubMed  CrossRef  Google Scholar 

  • Van den Dobbelsteen DJ, Nobel CSI, Samuelsson A, Orrenius S and Slater AFG (1996b) Glutathione metabolism during apoptosis. In: Oxidative stress, Cancer, AIDS and Neurodegenerative diseases. Marcel Dekker, New York, in press.

    Google Scholar 

  • Westendorp MO, Frank R, Ochsenbauer C, Strieker K, Dhein J, Walczak H, Debatin KM and Krammer PH (1995) Sensitisation of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature 375: 497–500.

    PubMed  CrossRef  CAS  Google Scholar 

  • Wolfe JT, Ross D and Cohen GM (1994) A role for metals and free radicals in the induction of apoptosis in thymocytes. FEBS Lett 352: 58–62.

    PubMed  CrossRef  CAS  Google Scholar 

  • Wyllie AH, Kerr JFR and Currie AR (1980) Cell death: The significance of apoptosis. Int Rev Cytol 68: 251–306.

    PubMed  CrossRef  CAS  Google Scholar 

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© 1997 Springer-Verlag Berlin Heidelberg

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van den Dobbelsteen, D.J., Nobel, C.S.I., Slater, A.F.G., Orrenius, S. (1997). Regulation and Mechanisms of Apoptosis in T Lymphocytes. In: Seiler, J.P., Vilanova, E. (eds) Applied Toxicology: Approaches Through Basic Science. Archives of Toxicology, vol 19. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60682-3_7

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  • DOI: https://doi.org/10.1007/978-3-642-60682-3_7

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