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Caspase Cascades in Chemically-Induced Apoptosis

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Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 500)

Abstract

Caspases play a central role in the execution phase of apoptosis and are responsible for many of the morphological features normally associated with this form of cell death. Toxicants appear to activate caspases primarily through perturbation of mitochondria and the subsequent formation of an Apaf-1/caspase-9 apoptosome complex. In this model, release of cytochrome, c.(cyt, c).from mitochondria is required to initiate assembly of the apoptosome. Release of cyt, c.is promoted by pro-apoptotic Bc1-2 family members, such as Bax, Bak and Bid, and inhibited by anti-apoptotic Bc1-2 proteins, including Bc1-2 and Bcl-xL. Toxicants may also, in some cases, upregulate death receptors and their cognate ligands leading to autocrine/paracrine-related apoptosis through assembly of Death Inducing Signaling Complexes (DISCs) and activation of caspase-8. Each of these basic caspase cascades will be discussed in detail.

Keywords

Endoplasmic Reticulum Stress Death Receptor Mitochondrial Permeability Transition Pore Death Domain Intermembrane Space 
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

  1. 1.
    Steller, H., Mechanisms and genes of cellular suicide, Science.267: 1445 (1995)PubMedCrossRefGoogle Scholar
  2. 2.
    Jacobson, M. D., Weil, M., Raff, M. C., Programmed cell death in animal development, Cell 88: 347 (1997)PubMedCrossRefGoogle Scholar
  3. 3.
    Kerr, J. F., Wyllie, A. H., Currie, A. R., Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics, Br. J. Cancer.26: 239 (1972)PubMedCrossRefGoogle Scholar
  4. 4.
    Thompson, C. B., Apoptosis in the pathogenesis and treatment of disease, Science.267: 1456 (1995)PubMedCrossRefGoogle Scholar
  5. 5.
    Searle, J., Lawson, T. A., Abbott, P. J., Harmon, B., Kerr, J. F., An electron-microscope study of the mode of cell death induced by cancer-chemotherapeutic agents in populations of proliferating normal and neoplastic cells, J. Pathol 116: 129 (1975)PubMedCrossRefGoogle Scholar
  6. 6.
    Kaufmann, S. H., Earnshaw, W. C., Induction of apoptosis by cancer chemotherapy, Exp. Cell Res. 256: 42 (2000)PubMedCrossRefGoogle Scholar
  7. 7.
    Bratton, S. B., Lau, S. S., Monks, T. J., The putative benzene metabolite 2,3,5-tris-(glutathion-Syl)hydroquinone depletes glutathione, stimulates sphingomyelin turnover, and induces apoptosis in HL-60 cells, Chem. Res. Toxicol. in press (2000)Google Scholar
  8. 8.
    Chrestensen, C. A., Starke, D. W., Mieyal, J. J., Acute cadmium exposure inactivates thioltransferase (glutaredoxin), inhibits intracellular reduction of protein-glutathionyl mixed disulfides, and initiates apoptosis, J Biol Chem.18:in press (2000)Google Scholar
  9. 9.
    Moran, J. L., Siegel, D., Sun, X. M., Ross, D., Induction of apoptosis by benzene metabolites in HL60 and CD34+ human bone marrow progenitor cells, Mol. Pharmacol.50: 610 (1996)PubMedGoogle Scholar
  10. 10.
    Zhan, Y., van de Water, B., Wang, Y., Stevens, J. L., The roles of caspase-3 and bcl-2 in chemically-induced apoptosis but not necrosis of renal epithelial cells, Oncogene.18: 6505 (1999)PubMedCrossRefGoogle Scholar
  11. 11.
    Arends, M. J., Wyllie, A. H., Apoptosis: mechanisms and roles in pathology, Int Rev Exp Pathol.32: 223 (1991)PubMedGoogle Scholar
  12. 12.
    Raffray, M., Cohen, G. M., Apoptosis and necrosis in toxicology: a continuum or distinct modes of cell death?, Pharmacol Ther. 75: 153 (1997)PubMedCrossRefGoogle Scholar
  13. 13.
    Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., et al., A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD, Nature.391: 43 (1998)PubMedCrossRefGoogle Scholar
  14. 14.
    Liu, X., Zou, H., Slaughter, C., Wang, X., DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis, Cell.89: 175 (1997)PubMedCrossRefGoogle Scholar
  15. 15.
    Sahara, S., Aoto, M., Eguchi, Y., Imamoto, N., Yoneda, Y., et al., Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation, Nature.401: 168 (1999)PubMedCrossRefGoogle Scholar
  16. 16.
    Susin, S. A., Lorenzo, H. K., Zamzami, N., Marzo, I., Snow, B. E., et al., Molecular characterization of mitochondria) apoptosis-inducing factor, Nature.397: 441 (1999)PubMedCrossRefGoogle Scholar
  17. 17.
    Fadok, V. A., Bratton, D. L., Rose, D. M., Pearson, A., Ezekewitz, R. A., et al., A receptor for phosphatidylserine-specific clearance of apoptotic cells, Nature.405: 85 (2000)PubMedCrossRefGoogle Scholar
  18. 18.
    Yuan, J., Shaham, S., Ledoux, S., Ellis, H. M., Horvitz, H. R., The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme, Cell.75: 641 (1993)PubMedCrossRefGoogle Scholar
  19. 19.
    Cohen, G. M., Caspases: the executioners of apoptosis, Biochem. J. 326:1 (1997)PubMedGoogle Scholar
  20. 20.
    Nicholson, D. W., Caspase structure, proteolytic substrates, and function during apoptotic cell death, Cell Death Differ. 6: 1028 (1999)CrossRefGoogle Scholar
  21. 21.
    Muzio, M., Stockwell, B. R., Stennicke, H. R., Salvesen, G. S., Dixit, V. M., An induced proximity model for caspase-8 activation, J. Biol. Chem. 273: 2926 (1998)PubMedCrossRefGoogle Scholar
  22. 22.
    Srinivasula, S. M., Ahmad, M., Fernandes-Alnemri, T., Alnemri, E. S., Autoactivation of procaspase-9 by Apaf-1 -mediated oligomerization, Mol. Cell.1: 949 (1998)PubMedCrossRefGoogle Scholar
  23. 23.
    Hengartner, M. O., Horvitz, H. R., Programmed cell death in Caenorhabditis elegans, Curr. Opin. Genet. Del.4: 581 (1994)CrossRefGoogle Scholar
  24. 24.
    Yang, X., Chang, H. Y., Baltimore, D., Essential role of CED-4 oligomerization in CED-3 activation and apoptosis, Science.281: 1355 (1998)PubMedCrossRefGoogle Scholar
  25. 25.
    Green, D. R., Reed, J. C., Mitochondria and apoptosis, Science.281: 1309 (1998)PubMedCrossRefGoogle Scholar
  26. 26.
    Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., et al., Cytochrome c and dATPdependent formation of Apaf-l/caspase-9 complex initiates an apoptotic protease cascade, Cell. 91: 479 (1997)PubMedCrossRefGoogle Scholar
  27. 27.
    Zou, H., Henzel, W. J., Liu, X., Lutschg, A., Wang, X., Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3, Cell.90: 405 (1997)PubMedCrossRefGoogle Scholar
  28. 28.
    Yeh, W. C., Hakem, R., Woo, M., Mak, T. W., Gene targeting in the analysis of mammalian apoptosis and TNF receptor superfamily signaling, Immunol. Rev.169: 283 (1999)PubMedCrossRefGoogle Scholar
  29. 29.
    Saleh, A., Srinivasula, S. M., Acharya, S., Fishel, R., Alnemri, E. S., Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation, J. Biol. Chem. 274:17941 (1999)PubMedCrossRefGoogle Scholar
  30. 30.
    Zou, H., Li, Y., Liu, X., Wang, X., An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9, J. Biol. Chem.274: 11549 (1999)PubMedCrossRefGoogle Scholar
  31. 31.
    Cain, K., Brown, D. G., Langlais, C., Cohen, G. M., Caspase activation involves the formation of the aposome, a large (approximately 700 kDa) caspase-activating complex, J. Biol. Chem. 274:22686 (1999)PubMedCrossRefGoogle Scholar
  32. 32.
    Cain, K., Bratton, S. B., Langlais, C., Walker, G., Brown, D. G., et al., Apaf-1 Oligomerizes into Biologically Active -700-kDa and Inactive --1.4- MDa Apoptosome Complexes, J. Biol. Chem. 275:6067 (2000)PubMedCrossRefGoogle Scholar
  33. 33.
    Qin, H., Srinivasula, S. M., Wu, G., Femandes-Alnemri, T., Alnemri, E. S., et al., Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1, Nature. 399: 549 (1999)PubMedCrossRefGoogle Scholar
  34. 34.
    Rodriguez, J., Lazebnik, Y., Caspase-9 and APAF-1 form an active holoenzyme, Genes Dew. 13: 3179 (1999)CrossRefGoogle Scholar
  35. 35.
    Hu, Y., Benedict, M. A., Ding, L., Nunez, G., Role of cytochrome c and dATP/ATP hydrolysis in Apaf1-mediated caspase- 9 activation and apoptosis, EMBO J. 18: 3586 (1999)PubMedCrossRefGoogle Scholar
  36. 36.
    Marzo, I., Brenner, C., Zamzami, N., Susin, S. A., Beutner, G., et al., The permeability transition pore complex. a target for apoptosis regulation by caspases and bcl-2-related proteins, J. Exp. Med. 187: 1261 (1998)PubMedCrossRefGoogle Scholar
  37. 37.
    Crompton, M., The mitochondrial permeability transition pore and its role in cell death, Biochem J.341: 233 (1999)PubMedCrossRefGoogle Scholar
  38. 38.
    Zamzami, N., Marchetti, P., Castedo, M., Hirsch, T., Susin, S. A., et al., Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis, FEBS Lett. 384: 53 (1996)PubMedCrossRefGoogle Scholar
  39. 39.
    Bossy-Wetzel, E., Newmeyer, D. D., Green, D. R., Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization, Embo J. 17: 37 (1998)PubMedCrossRefGoogle Scholar
  40. 40.
    Marzo, I., Susin, S. A., Petit, P. X., Ravagnan, L., Brenner, C., et al., Caspases disrupt mitochondrial membrane barrier function, FEBS Lett. 427: 198 (1998)PubMedCrossRefGoogle Scholar
  41. 41.
    Ichas, F., Mazat, J. P., From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low-to high-conductance state, Biochim Biophys Acta.1366:33 (1998)PubMedCrossRefGoogle Scholar
  42. 42.
    Adams, J. M., Cory, S., The Bd-2 protein family: arbiters of cell survival, Science.281: 1322 (1998)PubMedCrossRefGoogle Scholar
  43. 43.
    Minn, A. J., Velez, P., Schendel, S. L., Liang, H., Muchmore, S. W., et al., Bcl-xL forms an ion channel in synthetic lipid membranes, Nature.385: 353 (1997)PubMedCrossRefGoogle Scholar
  44. 44.
    Muchmore, S. W., Sattler, M., Liang, H., Meadows, R. P., Harlan, J. E., et al., X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death, Nature.381:335 (1996)PubMedCrossRefGoogle Scholar
  45. 45.
    Schendel, S. L., Montai, M., Reed, J. C., Bd-2 family proteins as ion-channels, Cell Death Differ. 5:372 (1998)PubMedCrossRefGoogle Scholar
  46. 46.
    Krajewski, S., Tanaka, S., Takayama, S., Schibler, M. J., Fenton, W., et al., Investigation of the subcellular distribution of the bc1–2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes, Cancer Res.53:4701 (1993)PubMedGoogle Scholar
  47. 47.
    Shimizu, S., Narita, M., Tsujimoto, Y., Bd-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC, Nature.399:483 (1999)PubMedCrossRefGoogle Scholar
  48. 48.
    Shimizu, S., Konishi, A., Kodama, T., Tsujimoto, Y., BH4 domain of antiapoptotic Bc1–2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondria] changes and cell death, Proc. Natl. Acad. Sci. U S A.97:3100 (2000)PubMedCrossRefGoogle Scholar
  49. 49.
    Shimizu, S., Tsujimoto, Y., Proapoptotic BH3-only Bc1–2 family members induce cytochrome c release, but not mitochondrial membrane potential loss, and do not directly modulate voltage-dependent anion channel activity, Proc. Natl. Acad. Sci. USA.97:577 (2000)PubMedCrossRefGoogle Scholar
  50. 50.
    Marzo, I., Brenner, C., Zamzami, N., Jurgensmeier, J. M., Susin, S. A., et al., Bax and adenine nucleotide translocator cooperate in the mitochondria] control of apoptosis, Science.281:2027 (1998)PubMedCrossRefGoogle Scholar
  51. 51.
    Antonsson, B., Conti, F., Ciavatta, A., Montessuit, S., Lewis, S., et al., Inhibition of Bax channel-forming activity by Bc1–2, Science.277:370 (1997)PubMedCrossRefGoogle Scholar
  52. 52.
    Matsuyama, S., Xu, Q., Velours, J., Reed, J. C., The Mitochondria FOF1-ATPase proton pump is required for function of the proapoptotic protein Bax in yeast and mammalian cells, Mol. Cell.3:327 (1998)CrossRefGoogle Scholar
  53. 53.
    Shimizu, S., Eguchi, Y., Kamiike, W., Funahashi, Y., Mignon, A., et al., Bd-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux, Proc. Natl. Acad. Sci. U SA.95:1455 (1998)CrossRefGoogle Scholar
  54. 54.
    Baffy, G., Miyashita, T., Williamson, J. R., Reed, J. C., Apoptosis induced by withdrawal of interleukin3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bc1–2 oncoprotein production, JBiol Chem.268:6511 (1993)Google Scholar
  55. 55.
    Lam, M., Bhat, M. B., Nunez, G., Ma, J., Distelhorst, C. W., Regulation of Bel-xi channel activity by calcium, J. Biol. Chem. 273:17307 (1998)PubMedCrossRefGoogle Scholar
  56. 56.
    Tournier, C., Hess, P., Yang, D. D., Xu, J., Turner, T. K., et al., Requirement of INK for stress-induced activation of the cytochrome c-mediated death pathway, Science.288:870 (2000)PubMedCrossRefGoogle Scholar
  57. 57.
    Kharbanda, S., Saxena, S., Yoshida, K., Pandey, P., Kaneki, M., et al., Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage, JBiol Chem.275:322 (2000)CrossRefGoogle Scholar
  58. 58.
    Ng, F. W., Shore, G. C., Bcl-XL cooperatively associates with the Bap31 complex in the endoplasmic reticulum, dependent on procaspase-8 and Ced-4 adaptor, J. Biol. Chem. 273:3140 (1998)PubMedCrossRefGoogle Scholar
  59. 59.
    Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., et al., Caspase-12 mediates endoplasmic-reticulumspecific apoptosis and cytotoxicity by amyloid-β, Nature.403:98 (2000)PubMedCrossRefGoogle Scholar
  60. 60.
    Ashkenazi, A., Dixit, V. M., Death receptors: signaling and modulation, Science.281:1305 (1998)PubMedCrossRefGoogle Scholar
  61. 61.
    Bratton, S. B., MacFarlane, M., Cain, K., Cohen, G. M., Protein complexes activate distinct caspase cascades in death receptor and stress-induced apoptosis, Exp. Cell Res. 256:27 (2000)PubMedCrossRefGoogle Scholar
  62. 62.
    Wallach, D., Varfolomeev, E. E., Malinin, N. L., Goltsev, Y. V., Kovalenko, A. V., et al., Tumor necrosis factor receptor and Fas signaling mechanisms, Annu. Rev. Immunol. 17:331 (1999)PubMedCrossRefGoogle Scholar
  63. 63.
    Medema, J. P., Scaffidi, C., Kischkel, F. C., Shevchenko, A., Mann, M., et al., FLICE is activated by association with the CD95 death-inducing signaling complex (DISC), EMBO J. 16:2794 (1997)PubMedCrossRefGoogle Scholar
  64. 64.
    Houghton, J. A., Harwood, F. G., Tillman, D. M., Thymineless death in colon carcinoma cells is mediated via fas signaling, Proc. Natl. Acad. Sci. USA.94:8144 (1997)PubMedCrossRefGoogle Scholar
  65. 65.
    Li, H., Zhu, H., Xu, C. J., Yuan, J., Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis, Cell.94:491 (1998)PubMedCrossRefGoogle Scholar
  66. 66.
    Strasser, A., Harris, A. W., Huang, D. C., Krammer, P. H., Cory, S., Bd-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis, EMBO J. 14:6136 (1995)PubMedGoogle Scholar
  67. 67.
    Scaffidi, C., Fulda, S., Srinivasan, A., Friesen, C., Li, F., et al., Two CD95 (APO-1/Fas) signaling pathways, EMBO J. 17:1675 (1998)PubMedCrossRefGoogle Scholar
  68. 68.
    Huang, D. C., Hahne, M., Schroeter, M., Frei, K., Fontana, A., et al., Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bc1–2 or Bcl-x(L), Proc. Natl. Acad. Sci. U S.96:14871 (1999).CrossRefGoogle Scholar

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© Springer Science+Business Media New York 2001

Authors and Affiliations

  1. 1.MRC Toxicology Unit, Hodgkin BuildingUniversity of LeicesterLeicesterUK

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