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Inhibition of Apoptosis In Mammalian Cell Culture

The Biotechnological Relevance of Limiting Cell Death

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Part of the book series: Cell Engineering ((CEEN,volume 1))

Abstract

When J.F. Enders first used primate cells to produce poliomyelitis virus in 1949, a multi-billion dollar industry was born. The realization that viruses could be attenuated in vitro for use as vaccines initiated attempts to develop large scale cultures of mammalian cells. In the 1970’s, two discoveries led to the expanded use of such cultures: (1) the advent of recombinant DNA technology meant that cell lines could be engineered to overexpress heterologous genes, and (2) the development of hybridoma cell lines provided a system capable of continuously secreting antibodies (Kohler and Milstein, 1975). Today, dozens of products including virus vaccines, antibodies, interferons, immunoregulators, hormones, and growth factors are manufactured by mammalian cells in culture; this number promises only to increase as our understanding of cellular processes grows.

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References

  • Al-Rubeai, M., Mills, D., and Emery, A.N. (1990). Electron microscopy of hybridoma cells with special regard to monoclonal antibody production. Cytotechnology 4, 13–28.

    PubMed  CAS  Google Scholar 

  • Al-Rubeai, M., Singh, R.P., Goldman, M.H., and Emery, A.N. (1995). Death mechanisms of animal cells in conditions of intensive cell-culture systems. Biotechnol. Bioeng. 45, 463–472.

    CAS  Google Scholar 

  • Alnemri, E. S., Robertson, N.M., Femandes, T.F., Croce, CM., and Litwack, G. (1992). Overexpressed full-length human BCL-2 extends the survival of baculovirus-infected Sf9 insect cells. Proc. Natl. Acad. Sci. USA 89, 7295–7299.

    PubMed  CAS  Google Scholar 

  • Baffy, G., Miyashita, T., Williamson, J.R., and Reed, J.C. (1993). Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production. J. Biol. Chem. 268, 6511–6519.

    PubMed  CAS  Google Scholar 

  • Beidler, D. R., Tewari, M., Friesen, P.D., Poirier, G., and Dixit, V.M. (1995). The baculovirus p35 protein inhibits Fas-and tumor necrosis factor-induced apoptosis. J. Biol. Chem. 270, 16526–16528.

    PubMed  CAS  Google Scholar 

  • Bessho, R., Matsubara, K., Kubota, M., Kuwakado, K., Hirota, H., Wakazono, Y., Lin, Y.W., Okuda, A., Kawai, M., Nishikomori, R., and Heike, T. (1994). Pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor kappa B (NF-kappa B) activation, prevents apoptosis in human promelocytic leukemia HL-60 cells and thymocytes. Biochem. Pharmacol. 48, 1883–9.

    PubMed  CAS  Google Scholar 

  • Beyette, J., Mason, G.G., Murray, R.A., Cohen, G.M., and Rivett, A.J. (1998). Proteasome activities decrease during dexamethasone-induced apoptosis of thymocytes. Biochem. J. 332, 315–320.

    PubMed  CAS  Google Scholar 

  • Bierau, H., Perani, A., Al-Rubeai, M., and Emery, A.N. (1998). A comparison of intensive cell culture bioreactors operating with Hybridomas modified for inhibited apoptotic response. J. Biotechnol. 62, 195–207.

    PubMed  CAS  Google Scholar 

  • Bissonnette, R. P., Echeverri, F., Mahboubi, A., and Green, D.R. (1992). Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature 359, 552–556.

    PubMed  CAS  Google Scholar 

  • Bliem, R., Konoptsky, K., and Katinger, H. (1991). Industrial animal cell reactor systems: Aspects of selection and evaluation. In A. Fiechter (ed.), Advances in Biochemical Engineering/Biotechnology Vol. 44, Springer-Verlag, Berlin, pp. 1–26.

    Google Scholar 

  • Boise, L. H., Gonzalez-Garcia, M., Postema, C.E., Ding, L., Lindsten, T., Turka, L.A., Mao, X., Nunez, G., and Thompson, C.B. (1993). bcl-x, a bcl-2 related gene that functions as a dominant regulator of apoptotic cell death. Cell 74, 598–608.

    Google Scholar 

  • Bortner, C. D., and Cidlowski, J.A. (1996). Absence of volume regulatory mechanisms contributes to the rapid activation of apoptosis in thymocytes. Am. J. Physiol. 271, C950–961.

    PubMed  CAS  Google Scholar 

  • Bossy-Wetzel, E., Newmeyer, D.D., and Green, D.R. (1998). Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization. EMBO J. 17, 37–49.

    PubMed  CAS  Google Scholar 

  • Bradham, C. A., Zian, T., Streetz, K., Trautwein, C., Brenner, D.A., and Lemasters, J.J. (1998). The mitochondrial permeability transition is required for tumor necrosis factor alpha-mediated apoptosis and cytochrome c release. Mol. Cell. Biol. 18, 6353–6364.

    PubMed  CAS  Google Scholar 

  • Butler, M. (1987) Animal Cell Technology: Principles and Products, Open University Press, London.

    Google Scholar 

  • Cartier, J. L., Hershberger, P.A., and Friesen, P.D. (1994). Suppression of apoptosis in insect cells stably transfected with Baculovirus p35: dominant interference by N-terminal sequences p35 1.76. J. Virol. 68, 7728–7737.

    PubMed  CAS  Google Scholar 

  • Chang, B.S., Minn, A.J., Muchmore, S.W., Fesik, S.W., and Thompson, C.B. (1997). Identification of a novel regulatory domain in Bcl-xL and Bcl-2. EMBO J. 16, 968–977.

    PubMed  CAS  Google Scholar 

  • Cheng, E. H.-Y., Nicholas, J., Bellows, D.S., Hayword, G.S., Guo, H-G., Reitz, M.S., and Hardwick, J.M. (1997a). A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc. Natl. Acad. Sci. USA 94, 690–694.

    PubMed  CAS  Google Scholar 

  • Cheng, E. H.-Y., Kirsch, D.G., Clem, R.J., Ravi, R., Kastan, M.B., Bedi, A., Ueno, K., and Hardwick, J.M. (1997b). Conversion of Bcl-2 to a Bax-like death effector by caspases. Science 278, 1966–1968.

    PubMed  CAS  Google Scholar 

  • Chiou, S. K., and White, E. (1998). Inhibition of ICE-like proteases inhibits apoptosis and increases virus production during adenovirus infection. Virology 244, 108–118.

    PubMed  CAS  Google Scholar 

  • Chung, J. D., Zabel, C., Sinskey, A.J., and Stephanopoulos, G. (1997). Extension of Sp2/0 hybridoma cell viability through interleukin-6 supplementation. Biotechnol. Bioeng. 55, 439–446.

    CAS  Google Scholar 

  • Clem, R. J., and Miller, L.K. (1994). Control of programmed cell death by the baculovirus genes p35 and lap. Mol. Cell. Biol. 14, 5212–5222.

    PubMed  CAS  Google Scholar 

  • Clem, R. J., Hardwick, J.M., and Miller, L.K. (1996). Anti-apoptotic genes of baculoviruses. Cell Death Diff. 3, 13–20.

    Google Scholar 

  • Clem, R. J., Cheng, E. H.-Y., Karp, C.L., Kirsch, D.G., Ueno, K., Takahashi, A., Kastan, M.B., Griffin, D.E., Earnshaw, W.C., Veliuona, M.A., and Hardwick, J.M. (1998). Modulation of cell death by Bcl-xL through caspase interaction. Proc. Natl. Acad. Sci. USA 95, 554–559.

    PubMed  CAS  Google Scholar 

  • Cossarizza, A., Franceschi, C, Monti, D., Salvioli, S., Bellesia, E., Rivabene, R., Biondo, L., Rainaldi, G., Tinari, A., and Malorni, W. (1995). Protective effect of N-acetylcysteine in tumor necrosis factor-alpha-induced apoptosis in U937 cells: the role of mitochondria. Exp. Cell Res. 220, 232–240.

    PubMed  CAS  Google Scholar 

  • Cotter, T. G., and Al-Rubeai, M. (1995). Cell death (apoptosis) in cell culture systems. Trends Biotechnol. 13, 150–154.

    PubMed  CAS  Google Scholar 

  • Crook, N. E., Clem, R.J., and Miller, L.K. (1993). An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J. Virol. 67, 2168–2174.

    PubMed  CAS  Google Scholar 

  • Cummings, M. C., Winterford, C.M., and Walker, N.I. (1997). Apoptosis. Am. J. Surg. Pathol. 21, 88–101.

    PubMed  CAS  Google Scholar 

  • Datte, R., Kojima, H., Banach, D., Bump, N.J., Talanian, R.V., Alnemri, E.S., Weichselbaum, R.R., Wong, W.W., and Kufe, D.W. (1997). Activation of a CrmA-insenshive, p35-sensitive pathway in ionizing radiation-induced apoptosis. J. Biol. Chem. 272, 1965–1969.

    Google Scholar 

  • Degli Esposti, M., and McLennan, H. (1998). Mitochondria and cells produce reactive oxygen species in virtual anaerobiosis: relevance to ceramide-induced apoptosis. FEBS Lett. 430, 338–342.

    PubMed  CAS  Google Scholar 

  • Dimmeler, S., Haendeler, J., Rippmann, V., Nehls, M., and Zeiher, A.M. (1996). Shear stress inhibits apoptosis of human endothelial cells. FEBS Lett. 399, 71–74.

    PubMed  CAS  Google Scholar 

  • DiStefano, D. J., Mark, G.E., and Robinson, D.K. (1996). Feeding of nutrients delays apoptotic death in fed-batch cultures of recombinant NS0 myeloma cells. Biotechnol. Lett. 18, 1067–1072.

    CAS  Google Scholar 

  • Dobbelstein, M., and Shenk, T. (1996). Protection against apoptosis by the vaccinia virus SPI-2 (B13R) gene product. J. Virol. 70, 6479–6485.

    PubMed  CAS  Google Scholar 

  • Duckett, C. S., Nava, V.E., Gedrich, R.W., Clem, R.J., VanDongen, J.L., Gilfillan, M.C., Shiels, H., Hardwick, J.M., and Thompson, C.B. (1996). A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J. 15, 2685–2694.

    PubMed  CAS  Google Scholar 

  • Duckett, C. S., Li, F., Wang, Y., Tomaselli, K.J., Thompson, C.B., and Armstrong, R.C. (1998). Human IAP-like protein regulates programmed cell death downstream of Bcl-xL and cytochrome c. Mol. Cell. Biol. 18, 608–615.

    PubMed  CAS  Google Scholar 

  • Duval, D., Demangel, C., Munier-Jolain, K., Miossec, S., and Geahel, I. (1991). Factors controlling cell proliferation and antibody production in mouse hybridoma cells: I. Influence of the amino acid supply. Biotechnol. Bioeng. 38, 561–570.

    CAS  Google Scholar 

  • Eagle, H. (1955). Nutrition needs of mammalian cells in tissue culture. Science 122, 501–504.

    PubMed  CAS  Google Scholar 

  • Eagle, H. (1959). Amino acid metabolism in mammalian cell cultures. Science 130, 432–437.

    PubMed  CAS  Google Scholar 

  • Enari, M., Hug, H., and Nagata, S. (1995). Involvement of an ICE-like protease in Fas-mediated apoptosis. Nature 375, 78–81.

    PubMed  CAS  Google Scholar 

  • Fassnacht, D., Rössing, S., Franěk, F., Al-Rubeai, M., and Pörtner, R. (1998). Effect of bcl-2 expression on hybridoma cell growth in serum-supplemented, protein-free and diluted media. Cytotechnology 26, 219–225.

    CAS  Google Scholar 

  • Fernandez, A., Marin, M.C., McDonnell, T.J., and Ananthaswamy, H.N. (1994). Differential sensitivity of normal and Ha-ras-transformed C3H mouse embryo fibroblasts to tumor necrosis factor: induction of bcl-2, c-myc, and manganese Superoxide dismutase in resistant cells. Oncogene 9, 2009–2017.

    PubMed  CAS  Google Scholar 

  • Franěk, F., and Dolníková, J. (1991a). Nucleosomes occuring in protein-free hybridoma cell cultures. Evidence for programmed cell death. FEBS Lett. 248, 285–287.

    Google Scholar 

  • Franěk, F., and Dolníková, J. (1991b). Hybridoma growth and monoclonal antibody production in iron-rich protein-free medium: effect of nutrient concentration. Cytotechnology 7, 33–38.

    PubMed  Google Scholar 

  • Franěk, F., and Chládkova-Srámková, K. (1995). Apoptosis and nutrition: involvement of amino acid transport system in repression of hybridoma cell death. Cytotechnology 18, 113–117.

    Google Scholar 

  • Franěk, F., and Srámková, K. (1996a). Cell suicide in starving hybridoma culture: survival-signal effect of some amino acids. Cytotechnology 21, 81–89.

    Google Scholar 

  • Franěk, F., and Srámková, K. (1996b). Cell suicide in starving hybridoma culture: survival-signal effecto fo some amino acids. Cytotechnology 21, 81–89.

    Google Scholar 

  • Fulda, S., Susin, S.A., Kroemer, G., and Debatin, K.M. (1998). Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells. Cancer Res. 58, 4453–4460.

    PubMed  CAS  Google Scholar 

  • Fussenegger, M., Schlatter, S., Dätwyler, S., Mazur, X., and Bailey, J.E. (1998). Controlled proliferation by multigene metabolic engineering enhances the productivity of Chinese hamster ovary cells. Nat. Biotech. 16, 468–472.

    CAS  Google Scholar 

  • Gagliardini, V., Fernandez, P.-A., Lee, R.K.K., Drexler, H.C.A., Rotello, R.J., Fishman, M.C., and Yuan, J. (1994). Prevention of vertebrate neuronal death by the crmA gene. Science 262, 826–828.

    Google Scholar 

  • Gerschenson, L. E., and Rotello, R. J. (1992). Apoptosis: a different type of cell death. FASEB J. 6, 2450–2455.

    PubMed  CAS  Google Scholar 

  • Grandgirard, D., Studer, E., Monney, L., Belser, T., Fellay, I., Bomer, C., and Michel, M.R. (1998). Alphaviruses induce apoptosis in Bel-2-overexpressing cells: evidence for a caspase-mediated proteolytic inactivation of Bcl-2. EMBO J. 17, 1268–1278.

    PubMed  CAS  Google Scholar 

  • Greenlund, L. J. S., Deckwerth, T.L., and Johnson, E.M. Jr. (1995). Superoxide dismutase delays neuronal apoptosis: a role for reactive oxygen species in programmed neuronal cell death. Neuron 14, 303–315.

    PubMed  CAS  Google Scholar 

  • Hardwick, J. M. (1997). Virus-induced apoptosis. Adv. Pharmacol. 41, 295–336.

    PubMed  CAS  Google Scholar 

  • Hardwick, J. M. (1998). Viral interference with apoptosis. Semin. Cell Dev. Biol. 9, 339–349.

    PubMed  CAS  Google Scholar 

  • Hashimoto, S., Ishii, A., and Yonehara, S. (1991). The Elb oncogene of adenovirus confers cellular resistance to cytotoxicity of tumor necrosis factor and monoclonal anti-Fas antibody. Int. Immunol. 17, 2835–2843.

    Google Scholar 

  • Hehner, S. P., Hofmann, T.G., Ratter, F., Dumont, A., Droge, W., and Schmitz, M.L. (1998). Tumor necrosis factor-alpha-induced cell killing and activation of transcription factor NF-kappaB are uncoupled in L929 cells. J. Biol. Chem. 273, 18117–18121.

    PubMed  CAS  Google Scholar 

  • Henderson, S., Huen, D., Rowe, M., Dawson, C., Johnson, G., and Rickinson, A. (1993). Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc. Natl. Acad. Sci. USA 90, 8479–8483.

    PubMed  CAS  Google Scholar 

  • Hockenbery, D. M., Oltvai, Z.N., Yin, X.-M., Milliman, C.L., and Korsmeyer, S.J. (1993). Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75, 241–251.

    PubMed  CAS  Google Scholar 

  • Hortelano, S., Dallaporta, B., Zamzami, N., Hirsch, T., Susin, S.A., Marzo, I., Bosca, L., and Kroemer, G. (1997). Nitric oxide induces apoptosis via triggering mitochondrial permeability transition. FEBS Lett. 410, 373–377.

    PubMed  CAS  Google Scholar 

  • Ichas, F., and Mazat, J.P. (1998). 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, 33–50.

    PubMed  CAS  Google Scholar 

  • Ink, B. S., Gilbert, C.S., and Evan, G.I. (1995). Delay of vaccinia virus-induced apoptosis in nonpermissive Chinese hamster ovary cells by the cowpox virus CHOhr and adenovirus ElB 19K genes. J. Virol. 69, 661–668.

    PubMed  CAS  Google Scholar 

  • Itoh, Y., Ueda, H., and Suzuki, E. (1995). Overexpression of bcl-2, apoptosis suppressing gene: prolonged viable culture period of hybridoma and enhanced antibody production. Biotech. Bioeng. 48, 118–122.

    CAS  Google Scholar 

  • Jacobson, M. D., and Raff, M.C. (1995). Programmed cell death and Bcl-2 protection in very low oxygen. Nature 374, 814–816.

    PubMed  CAS  Google Scholar 

  • Jacobson, M. D. (1996). Reactive oxygen species and programmed cell death. Trends Biochem. Sci. 21, 83–86.

    PubMed  CAS  Google Scholar 

  • Jobses, I., Marten, D., and Tramper, J. (1991). Lethal events during gas sparging in animal cell culture. Biotechnol. Bioeng. 37, 484–490.

    CAS  Google Scholar 

  • Kerr, J. F. R., Wyllie, A.H., and Currie, A.R. (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26, 239–257.

    PubMed  CAS  Google Scholar 

  • Kluck, R. M., Bossy-Wetzel, E., Green, D.R., and Newmeyer, D.D. (1997). The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275, 1132–1136.

    PubMed  CAS  Google Scholar 

  • Köhler, G., and Milstein, C. (1975). Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495–497.

    PubMed  Google Scholar 

  • Kroemer, G., Zamzami, N., and Susin, S.A. (1997). Mitochondrial control of apoptosis. Immunol. Today 18, 44–51.

    PubMed  CAS  Google Scholar 

  • Levine, B., Huang, Q., Isaacs, J.T., Reed, J.C., Griffin, D.E., and Hardwick, J.M. (1993). Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature 361, 739–742.

    PubMed  CAS  Google Scholar 

  • Liao, C. L., Lin, Y.L., Wang, J.J., Huang, Y.L., Yeh, C.T., Ma, S.H., and Chen, L.K. (1997). Effect of enforced expression of human bcl-2 on Japanese encephalitis virus-induced apoptosis in cultured cells. J.Virol. 71, 5963–5971.

    PubMed  CAS  Google Scholar 

  • Lin, K.-L, Lee, S.-H., Narayanan, R., Baraban, J.M., Hardwick, J.M., and Ratan, R.R. (1995). Thiol agents and bcl-2 identify an alphavirus-induced apoptotic pathway that requires activation of the transcription factor NF-kappa B. J. Cell Biol. 131, 1149–1161.

    PubMed  CAS  Google Scholar 

  • Liston, P., Roy, N., Tamai, K., Lefebvre, C., Baird, S., Cherton-Horvat, G., Farahani, R., McLean, M., Ikeda, J, MacKenzie, A., and Korneluk, R.G. (1996). Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 379, 349–353.

    PubMed  CAS  Google Scholar 

  • Lundstrom, K., Pralong, W., and Martinou, J.-C. (1997). Anti-apoptotic effect of Bcl-2 overexpression in RIN cells infected with Semliki Forest virus. Apoptosis 2, 189–191.

    PubMed  CAS  Google Scholar 

  • Malomi, W., Rivabene, R., Santini, M.T., and Donelli, G. (1993). N-acetylcysteine inhibits apoptosis and decreases viral particles in HIV-chronically infected U937 cells. FEBS Lett. 327, 75–8.

    Google Scholar 

  • Marchetti, P., Castedo, M., Susin, S.A., Zamzami, N., Hirsch, T., Haeffner, A., Hirsch, F., Geuskens, M., and Kroemer, G. (1996). Mitochondrial permeability transition is a central coordinating event of apoptosis. J.Exp. Med. 184, 1155–1160.

    PubMed  CAS  Google Scholar 

  • Martin, S. J., Newmeyer, D.D., Mathias, S., Farschon, D.W., Wang, H.G., Reed, J.C., Kolesnick, R.N., and Green, D.R. (1995). Cell-free reconstitution of Fas-, UV radiation-and ceramide-induced apoptosis. EMBO J. 14, 5191–5200.

    PubMed  CAS  Google Scholar 

  • Martinou, I., Fernandez, P.-A., Missotten, M., White, E., Allet, B., Sadoul, R., and Martinou, J.-C. (1995). Viral proteins E1B19K and p35 protect sympathetic neurons from cell death induced by NGF deprivation. J. Cell Biol. 128, 201–208.

    PubMed  CAS  Google Scholar 

  • Marzo, I., Brenner, C., and Kroemer, G. (1998). The central role of the mitochondrial megachannel in apoptosis: evidence obtained with intact cells, isolated mitochondria, and purified protein complexes. Biomed. Pharmacother. 52, 248–251.

    PubMed  CAS  Google Scholar 

  • Mastrangelo, A. J., Hardwick, J.M., and Betenbaugh, M.J. (1996). Bcl-2 inhibits apoptosis and extends recombinant protein production in cells infected with Sindbis viral vectors. Cytotechnology 22, 169–178.

    CAS  Google Scholar 

  • Mastrangelo, A. J., and Betenbaugh, M.J. (1998). Overcoming apoptosis: new methods for improving protein expression systems. Trends Biotechnol. 16, 88–95.

    PubMed  CAS  Google Scholar 

  • Matthews, C. C., and Feldman, E.L. (1996). Insulin-like growth factor I rescues SH-SY5Y human neuroblastoma cells from hypertonic induced programmed cell death. J. Cell. Physiol. 166, 323–331.

    PubMed  CAS  Google Scholar 

  • Mayer, M., and Noble, M. (1994). N-Acetyl-L-cysteine is a pluripotent protector against cell death and enhancer of trophic factor-mediated cell survival in vitro. Proc. Natl. Acad. Sci. USA 91, 7496–7500.

    PubMed  CAS  Google Scholar 

  • McCarthy, N. J., Hazlewood, S.A., Huen, D.S., Rickinson, A.B., and Williams, G.T. (1996). The Epstein-Barr virus gene BHRF1, a homologue of the cellular oncogene Bcl-2, inhibits apoptosis induced by gamma radiation and chemotherapeutic drugs, in S. Gupta and J.J. Cohen (eds.) Mechamisms of Lymphocyte Activation and Immune Regulation VI: Cell Cycle and Programmed Cell Death in the Immune System, Plenum Press, New York, pp. 83–97.

    Google Scholar 

  • McColl. K. S., He, H., Zhong, H., Whitacre, C.M., Berger, N.A., and Distelhorst, C.W. (1998). Apoptosis induction by the glucocorticoid hormone dexamethasone and the calcium-ATPase inhibitor thapsigargin involves Bcl-2 regulated caspase activation. Mol. Cell. Endocrinol. 139, 229–238.

    PubMed  CAS  Google Scholar 

  • McGowan, A. J., Femandes, R.S., Samali, A., and Cotter, T.G. (1996). Anti-oxidants and apoptosis. Biochem. Soc. Trans. 24, 229–33.

    PubMed  CAS  Google Scholar 

  • McLachlin, J. R., and Miller, L.K. (1997). Stable transformation of insect cells to coexpress a rapidly selectable marker gene and an inhibitor of apoptosis. In Vitro Cell. Dev. Biol. 33, 575–579.

    CAS  Google Scholar 

  • Mercille, S., Johnson, M., Lemieux, R., and Massie, B. (1994). Filtration-based perfusion of hybridoma cultures in protein-free medium: reduction of membrane fouling by medium supplementation with DNasel. Biotechnol. Bioeng. 43, 833–846.

    CAS  Google Scholar 

  • Mercille, S., and Massie, B. (1994a). Induction of apoptosis in nutrient-deprived cultures of hybridoma and myeloma cells. Biotechnol. Bioeng. 44, 1140–1154.

    CAS  Google Scholar 

  • Mercille, S., and Massie, B. (1994b). Induction of apoptosis in oxygen-deprived cultures of hybridoma cells. Cytotechnology 15, 117–128.

    PubMed  CAS  Google Scholar 

  • Mercille, S., and Massie, B. (1998). Apoptosis-resistant NS/0-E1B-19K myeloma cells exhibit increased viability and chB43 monoclonal antibody productivity using cell cycle modulators. Cytotechnology In Press.

    Google Scholar 

  • Mercille, S., and Massie, B. (1999). Apoptosis-resistant ElB-19K-expressing NS/0 myeloma cells exhibit increased viability and chimeric antibody productivity under perfusion culture. Biotechnol. Bioeng. In Press.

    Google Scholar 

  • Mercille, S., Jolicoeur, P., Gervais, C., Paquette, D., Mosser, D.D., and Massie, B. (1999). Dose-dependent reduction of apoptosis in nutrient-limited cultures of NS/0 myeloma cells transfected with the E1B-19K adenoviral gene. Biotechnol. Bioeng. In Press.

    Google Scholar 

  • Mignotte, B., and Vayssiere, J.-L. (1998). Mitochondria and apoptosis. Eur. J. Biochem. 252, 1–15.

    PubMed  CAS  Google Scholar 

  • Miller, L. K. (1997). Baculovirus interaction with host apoptotic pathways. J. Cell. Physiol. 173, 178–182.

    PubMed  CAS  Google Scholar 

  • Mitchell-Logean, C., and Murhammer, D.W. (1997). bcl-2 expression in Spodoptera frugiperda Sf-9 and Trichoplusia ni BTI-Tn-5Bl-4 insect cells: effect on recombinant protein expression and cell viability. Biotechnol. Bioeng. 56, 380–388.

    CAS  Google Scholar 

  • Miura, M., Friedlander, R.M., and Yuan, J. (1995). Tumor necrosis factor-induced apoptosis is mediated by a Crm-A-sensitive cell death pathway. Proc. Natl. Acad. Sci. USA 92, 8318–8322.

    PubMed  CAS  Google Scholar 

  • Miyashita, T., and Reed, J.C. (1992). bcl-2 gene transfer increases relative resistance of S49.1 and WEH 17.2 lymphoid cells to cell death and DNA fragmentation induced by glucocorticoids and multiple chemotherapeutic drugs. Cancer Res. 52, 5407–5411.

    PubMed  CAS  Google Scholar 

  • Murray, K., Ang, C.-E., Gull, K., Hickman, J.A., and Dickson, A.J. (1996). NSO myeloma cell death: influence of bcl-2 overexpression. Biotechnol. Bioeng. 51, 298–304.

    CAS  Google Scholar 

  • Nava, V. E., Rosen, A., Veliuona, M.A., Clem, R.J., Levine, B., and Hardwick, J.M. (1998). Sindbis virus induces apoptosis through a caspase-dependent, CrmA-sensitive pathway. J. Virol. 72, 452–459.

    PubMed  CAS  Google Scholar 

  • Oh, S. K. W., Vig, P., Chua, F.K.F, Teo, W.K., and Yap, M.S.G. (1993). Substantial overproduction of antibodies by applying osmotic pressure and sodium butyrate. Biotechnol. Bioeng. 42, 601–610.

    CAS  Google Scholar 

  • Oltvai, Z. N., Milliman, C.L., and Korsmeyer, S.J. (1993). Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death. Cell 74, 609–619.

    PubMed  CAS  Google Scholar 

  • Ozturk, S. S., and Palsson, B.O. (1991). Effect of medium osmolarity on hybridoma growth, metabolism and antibody production. Biotechnol. Bioeng. 37, 989–993.

    CAS  Google Scholar 

  • Pastorino, J. G., Synder, J.W., Serroni, A., Hoek, J.B., and Farber, J.L. (1993). Cyclosporin and carnitine prevent the anoxic death of cultured hepatocytes by inhibiting the mitochondrial permeability transition. J. Biol. Chem. 268, 13791–13798.

    PubMed  CAS  Google Scholar 

  • Pastorino, J. G., Simbula, G., Yamamoto, K., Glascott, P.A. Jr., Rothman, R.J., and Farber, J.L. (1996). The cytotoxicity of tumor necrosis factor depends on induction of the mitochondrial permeability transition. J. Biol. Chem. 271, 29792–29798.

    PubMed  CAS  Google Scholar 

  • Perani, A., Singh, R.P., Chauhan, R., and Al-Rubeai, M. (1998). Variable functions of bcl-2 in mediating bioreactor stress-induced apoptosis in hybridoma cells. Cytotechnology In Press.

    Google Scholar 

  • Perreault, J., and Lemieux, R. (1993). Essential role of optimal protein synthesis in preventing the apoptotic death of cultured B cell hybridomas. Cytotechnology 13, 99–105.

    PubMed  CAS  Google Scholar 

  • Pervaiz, S., Hirpara, J.L., and Clement, M.V. (1998). Caspase proteases mediate apoptosis induced by anticancer agent preactivated MC540 in human tumor cells. Cancer Lett. 128, 11–22.

    PubMed  CAS  Google Scholar 

  • Petronini, P. G., Urbani, S., Alfieri, R., Borghetti, A.F., and Guidotti, G.G. (1996). Cell susceptibility to apoptosis by glutamine deprivation and rescue: survival and apoptotic death in cultured lymphoma-leukemia cell lines. J. Cell Physiol. 169, 175–185.

    PubMed  CAS  Google Scholar 

  • Prior, C. P., Doyle, K.R., Duffy, S.A., Hope, J.A., Moellcring, BJ., Prior, G.M., Scott, R.W., and Tolbert, W.R. (1989). The recovery of highly purified biopharmaceuticals from perfusion cell culture bioreactors. J. Parent Sci. Tech. 43, 15–23.

    CAS  Google Scholar 

  • Pugachev, K. V., and Frey, T.K. (1998). Rubella virus induces apoptosis in cultured cells. Virology 250, 359–370.

    PubMed  CAS  Google Scholar 

  • Qi, X. M., He, H., Zhong, H., and Distelhorst, C.W. (1997). Baculovirus p35 and Z-VAD-fmk inhibit thapsigargin-induced apoptosis of breast cancer cells. Oncogene 15, 1207–1212.

    PubMed  CAS  Google Scholar 

  • Qin, S., Minami, Y., Kurosaki, T., and Yamamura, H. (1997). Distinctive functions of Syk and Lyn in mediating osmotic stress-.and ultraviolet C irradiation-induced apoptosis in chicken B cells. J. Biol. Chem. 272, 17994–17999.

    PubMed  CAS  Google Scholar 

  • Rabizadeh, S., LaCount, DJ., Friesen, P.D., and Bredesen, D.E. (1993). Expression of the baculovinis p35 gene inhibits mammalian neural cell death. J. Neurochem. 61, 2318–2321.

    PubMed  CAS  Google Scholar 

  • Reddy, S., and Miller, W.M. (1994). Effects of abrupt and gradual osmotic stress on antibody production and content in hybridoma cells that differ in production kinetics. Biotechnol. Prog. 10, 165–173.

    PubMed  CAS  Google Scholar 

  • Reed, J. C. (1994). Bcl-2 and the regulation of programmed cell death. J. Cell Biol. 124, 1–6.

    PubMed  CAS  Google Scholar 

  • Rossé, T., Olivier, R., Monney, L., Rager, M, Conus, S., Felley, I., Jansen, B., and Borner, C. (1998). Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Nature 391, 496–499.

    PubMed  Google Scholar 

  • Sarin, A., Wu, M.L., and Henkart, P.A. (1996). Different interleukin-1 beta converting enzyme (ICE) family protease requirements for the apoptotic death of T lymphocytes triggered by diverse stimuli. J. Exp. Med. 184, 2445–2550.

    PubMed  CAS  Google Scholar 

  • Scallan, M. F., Allsopp, T.E., and Fazakerley, J.K. (1997). bcl-2 acts early to restrict Semliki Forest virus replication and delays virus-induced programmed cell death. J. Virol. 71, 1583–1590.

    PubMed  CAS  Google Scholar 

  • Schafer, R., Karbach, K., and Hoppe, J. (1998). Multiple intracellular pathways interfere with the activation of a CPP32-like protease induced by serum deprivation of AKR-2B cells. Exp. Cell Res. 240, 28–39.

    PubMed  CAS  Google Scholar 

  • Sheshagiri, S., and Miller, L.K. (1997). Baculovirus inhibitors of apoptosis (IAPs) block activation of Sf-caspase-1. Proc. Natl. Acad. Sci. USA 94, 13606–13611.

    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-x,. Nature 374, 811–813.

    PubMed  CAS  Google Scholar 

  • Simpson, N., Milner, A.N., and Al-Rubeai, M. (1997). Preventaion of hybridoma cell death by bcl-2 during sub-optimal culture conditions. Biotechnol. Bioeng. 54, 1–16.

    CAS  Google Scholar 

  • Simpson, N. H., Singh, R.P., Perani, A., Goldenzon, C., and Al-Rubeai, M. (1998). In hybridoma cultures, deprivation of any single amino acid leads to apoptotic death, which is suppressed by the expression of the bcl-2 gene. Biotechnol. Bioeng. 59, 90–98.

    PubMed  CAS  Google Scholar 

  • Singh, R. P., Al-Rubeai, M., Gregory, C.D., and Emery, A.N. (1994). Cell death in bioreactors: A role for apoptosis. Biotechnol. Bioeng. 44, 720–726.

    CAS  Google Scholar 

  • Singh, R. P., Emery, A.N., and Al-Rubeai, M. (1996). Enhancement of survivability of mammalian cells by overexpression of the apoptosis-suppressor gene bcl-2. Biotechnol. Bioeng. 52, 166–175.

    CAS  Google Scholar 

  • Singh, R. P., Finka, G., Emery, A.N., and Al-Rubeai, M. (1997). Apoptosis and its control in cell culture systems. Cylotechnology 23, 87–93.

    Google Scholar 

  • Slater, A. F. G., Kimland, M., Jiang, S.A., and Orrenius, S. (1995). Constitutive nuclear NF-kappa-B/rel DNA-binding activity of rat thymocytes is increased by stimuli that promote apoptosis, but not inhibited by pyrrolidine dithiocarbamate. Biochem. J. 312, 833–838.

    PubMed  CAS  Google Scholar 

  • Strasser, A., and Anderson, R.L. (1995). Bcl-2 and thermotolerance cooperate in cell survival. Cell Growth Differ. 6, 799–805.

    PubMed  CAS  Google Scholar 

  • Sugimoto, A., Friesen, P.D., and Rothman, J.H. (1994). Baculovirus p35 prevents developmentally programmed cell death and rescues a ced-9 mutant in the nematode Caenorhabditis elegans. EMBO J. 13, 2023–2028.

    CAS  Google Scholar 

  • Susin, S. A., Zamzami, N., Castedo, M., Hirsch, T., Marchetti, P., Macho, A., Daugas, E., Geuskens, M., and Kroemer, G. (1996). Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J. Exp. Med. 184, 1331–1341.

    PubMed  CAS  Google Scholar 

  • Suzuki, E., Terada, S., Ueda, H., Fujita, T., Komatsu, T., Takayama, S., and Reed, J.C. (1997). Establishing apoptosis resistant cell lines for improving protein productivity of cell culture. Cytotechnology 23, 55–59.

    CAS  Google Scholar 

  • Takayama, S., Cazals-Hatem, D.L., Kitada, S., Tanaka, S., Miyashita, T., and Hovey, L.R. (1994). Evolutionary conservation of function among mammalian, avian, and viral homologs of the Bcl-2 oncoprotein. DNA Cell Biol. 13, 679–692.

    PubMed  CAS  Google Scholar 

  • Talley, A. K., Dewhurst, S., Perry, S.W., Dollard, S.C., Gummuluru, S., Fine, S.M., New, D., Epstein, L.G., Gendelman, H.E., and Gelbard, H.A. (1995). Tumor necrosis factor alpha-induced apoptosis in human neuronal cells: protection by the antioxidant N-Acetylcysteine and the genes bcl-2 and crmA. Mol. Cell. Biol. 15, 2359–2366.

    PubMed  CAS  Google Scholar 

  • Tarodi, B., Subramanian, T., and Chinnadurai, G. (1994). Epstein-Barr virus BHRF1 protein protects against cell death induced by DNA-damaging agents and heterologous viral infection. Virology 201, 404–407.

    PubMed  CAS  Google Scholar 

  • Terada, S., Fukuoka, K., Fujita, T., Komatsu, T., Takayama, S., Reed, J.C., and Suzuki, E. (1997). Anti-apoptotic genes, bag-1 and bcl-2, enabled hybridoma cells to survive under treatment for arresting cell cycle. Cytotechnology 25, 17–23.

    PubMed  CAS  Google Scholar 

  • Tewari, M., and Dixit, V.M. (1995). Fas-and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product. J. Biol. Chem. 270, 3255–3260.

    PubMed  CAS  Google Scholar 

  • Tewari, M., Quan, L.T., O’Rourke, K., Desnoyers, S., Zeng, Z., Beidler, D.R., Poirier, G.G., Slavesen., G.S., and Dixit, V.M. (1995). Yama/CPP32 beta, a mammalian homolog of CED-3, is a Crm-A-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polyermase. Cell 81, 801–809.

    PubMed  CAS  Google Scholar 

  • Thomas, J. N. (1990). Mammalian cell physiology, A. Lubiniecki (ed.), Bioprocess Technology, Vol. 10, Marcel Dekker, New York. pp. 93–145.

    Google Scholar 

  • Thornberry, N. A., and Lazebnik, Y. (1998). Caspases: enemies within. Science 281, 1312–1316.

    PubMed  CAS  Google Scholar 

  • Tsai, J. C., Jain, M., Hsieh, J.M., Lee, W.S., Yoshizumi, M., Patterson, C., Perrella, M.A., Cooke, C., Wand, H., Haber, E., Schlegel, R., and Lee, M.E. (1996). Induction of apoptosis by pyrrolidinedithiocarbamate and N-acetylcysteine in vascular smooth muscle cells. J. Biol. Chem. 271, 3667–3670.

    PubMed  CAS  Google Scholar 

  • Tsujimoto, Y., Finger, L.R., Yunis, J., Nowell, P.C., and Croce, CM. (1984). Cloning of the chromosome breakpoint of neoplastic B cells with the t(14:18) chromosome translocation. Science 226, 1097–1099.

    PubMed  CAS  Google Scholar 

  • Vander Heiden, M. G., Chandel, N.S., Williamson, E.K., Schumacher, P.T., and Thompson, C.B. (1997). Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell 91, 627–637.

    Google Scholar 

  • Vaux, D. L., and Weissman, I.L. (1988). Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335, 440–442.

    PubMed  CAS  Google Scholar 

  • Vomastek, V., and FranSk, F. (1993). Kinetics of development of spontaneous apoptosis in B cell hybridoma cultures. Immunol. Lett. 35, 19–24.

    PubMed  CAS  Google Scholar 

  • Wang, L., Miura, M., Bergeron, L., Zhu, H., and Yuan, J. (1994). Ich-1 and ICE/ced-3 related gene, encodes both positive and negative regulators of programmed cell death. Cell 78, 739–750.

    PubMed  CAS  Google Scholar 

  • Waring, P., and Beaver, J. (1996). Cyclosporin A rescues thymocytes from apoptosis induced by very low concentrations of thapsigargin: effects on mitochondrial function. Exp. Cell Res. 227, 264–276.

    PubMed  CAS  Google Scholar 

  • White, E., Sabbatini, P., Debbas, M, Wold, W.S.M., Rusher, D.I., and Gooding, L.R. (1992). The 19-kilodalton Adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor a. Mol. Cell. Biol. 12, 2570–2580.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Wong, G. H. W., Elwell, J.H., Oberley, L.W., and Goeddel, D.V. (1989). Manganous Superoxide dismutase is essential for cellular resistance to cytotoxicity of tumor necrosis factor. Cell 58, 923–931.

    PubMed  CAS  Google Scholar 

  • Yang, J., Liu, X., Bhalla, K., Kim, C.N., Ibrado, A.M., Cai, J., Peng, T-I., Jones, D.P., and Wang, X. (1997). Prevention of apoptosis by Bcl-2: release of cylochrome c from mitochondria blocked. Science 275, 1129–1132.

    PubMed  CAS  Google Scholar 

  • Yuan, J., Shaham, S., Ledoux, S., Ellis, H.M., and Horvitz, H.R. (1993). The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-lβ-converting enzyme. Cell 75, 641–652.

    PubMed  CAS  Google Scholar 

  • Zamzami, N., Marchetti, P., Castedo, M., Hirsch, T., Susin, S.A., Masse, B., and Kroemer, G. (1996a). Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis. FEBS Lett. 384, 53–57.

    PubMed  CAS  Google Scholar 

  • Zamzami, N., Susin, S.A., Marchetti, P., Hirsch, T., Castedo, M., and Kroemer, G. (1996b). Mitochondrial control of nuclear apoptosis. J. Exp. Med. 183, 1533–1544.

    PubMed  CAS  Google Scholar 

  • Zamzami, N., Hirsch, T., Dallaporta, B., Petit, P.X., and Kroemer, G. (1997). Mitochondrial implications in accidental and programmed cell death: apoptosis and necrosis. J. Bioeng. Biomembr. 29, 185–193.

    CAS  Google Scholar 

  • Zhivotovsky, B., Burgess, D.H., and Orrenius, S. (1996). Proteases in apoptosis. Experimentia 52, 968–978.

    CAS  Google Scholar 

  • Zhivotovsky, B., Orrenius, S., Brustugun, O.T., and Døskeland, S.O. (1998). Injected cytochrome c induces apoptosis. Nature 391, 449–450.

    PubMed  CAS  Google Scholar 

  • Zhou, Q., Snipas, S., Orth, K., Muzio, M., Dixit, V.M., and Salvesen, G.S. (1997). Target protease specificty of the viral serpin crmA. J. Biol. Chem. 272, 7797–7800.

    PubMed  CAS  Google Scholar 

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Mastrangelo, A.J. (1999). Inhibition of Apoptosis In Mammalian Cell Culture. In: Al-Rubeai, M. (eds) Cell Engineering. Cell Engineering, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-0-585-37971-5_6

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