Abstract
An uncontrolled and sustained increase in cytosolic Ca2+ concentration has been implicated as an early event in the developement of anoxic or toxic cell injury.
More recently it has become clear that an elevation of cytosolic Ca2+ is also involved in programmed cell death in the immune system. Here, we review some of our recent studies and provide further evidence for the role of Ca2+ in cell killing.
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References
Carafoli, E. (1987). Intracellular Ca2+ homeostasis. Ann. Rev. Biochem. 56, 395–433.
Chien, K.R., Pfau, R.G. and Farber, J.L. (1979). Ischemic myocardiac cell injury. Prevention by chlorpromazine of an accelerated phospholipid degradation and associated membrane dysfunction. Am. J. Pathol. 97, 505–530.
Dypbukt-Källman, J., Thor, H. and Nicotera, P. (1990). Intracellular Ca2+ chelators prevent DNA damage and protect hepatoma 1c1c7 cells from killing by a redox cycling quinone. Free Rad. Res. Comm. in press.
Farber, J.L. and Young, E.E. (1981). Accelerated phospholipid degradation in anoxic rat hepatocytes. Arch. Biochem. Biophys. 221, 312–320.
Fesus, L., Thomazy, V., Autuori, F., Ceru, M.P., Tarcsa, E. and Piacentini, M. (1989). Apoptotic hepatocytes become insoluble in detergents and chaotropic agents as a result of transglutaminase action. FEBS Lett. 245, 150–154.
Glende, E.A. Jr and Pushpendran, K.C. (1986). Activation of phospholipase A2 by carbon tetrachloride in isolated rat hepatocytes. Biochem. Pharmacol. 35, 3301–3307.
Jewell, S.A., Bellomo, G., Thor, H., Orrenius, S. and Smith, M.T. (1982). Bleb formation in hepatocytes during drug metabol:sm is caused by disturbances in thiol and calcium ion homeostasis. Science 217, 1257–1259.
Jones, D.P., McConkey, D.J., Nicotera, P. and Orrenius, S. (1989). Calcium-activated DNA fragmentation in rat liver nuclei. J. Biol. Chem. 264, 6398–6403.
McConkey, D.J., Hartzell, P., Duddy, S.K., Häkansson, H. and Orrenius, S. (1988). 2,3,7,8,-Tetrachlorodibenzo-p-dioxin kills immature thy mocytes by Ca2+ mediated endonuclease activation. Science 242, 256–259.
McConkey, D.J., Hartzell, P., Jondal, M. and Orrenius, S. (1989a). Inhibition of DNA fragmentation in thymocytes and isolated thymocyte nuclei by agents that stimulate protein kinase C. J. Biol. Chem. 264, 13399–13402.
McConkey, D.J., Nicotera, P., Hartzell, P., Bellomo, G., Wyllie, A.H. and Orrenius, S. (1989b). Glucocorticoids activate a suicide process in thymocytes through an elevation of cytosolic Ca2+ concentration. Arch. Biochem. Biophys. 269, 365–370.
Mirabelli, F., Salis, A., Vairetti, M., Bellomo, G., Thor, H. and Orrenius, S. (1989). Cytoskeletal alterations in human platelets exposed to oxidative stress are mediated by oxidative and Ca2+-dependent mechanisms. Arch. Biochem. Biophys. 270, 478–488.
Nicotera, P., Hartzell, P., Baldi, C., Svensson, S.-A., Bellomo, G. and Orrenius, S. (1986). Cystamine induces toxicity in hepatocytes through the elevation of cytosolic Ca2+ and the stimulation of a nonlysosomal proteolytic system. J. Biol. Chem. 261, 14628–14635.
Nicotera, P., McConkey, D.J., Jones, D. and Orrenius, S. (1989). ATP simulates Ca2+ uptake and increases the free Ca2+ concentration in isolated rat liver nuclei. Proc. Natl. Acad. Sci. USA 86, 453–457.
Nicotera, P., Thor, H. and Orrenius, S. (1988). Cytosolic free Ca2+ and cell killing in hepatoma 1c1c7 cells exposed to chemical anoxia. FASEB J. 3, 59–64.
Orrenius, S. and Bellomo, G. (1986). Toxicological implications of perturbation of Ca2+ homeostasis in hepatocytes. In Calcium and Cell Function ( W.Y. Cheung, Ed.), Vol. VI, pp. 185–208. Academic Press, Orlando, Florida, USA.
Orrenius, S., McConkey, D.J., Bellomo, G. and Nicotera, P. (1989). Role of Ca2+ in toxic cell killing. Trends Pharmacol. Sci. 10, 281–285.
Poenie, M., Tsien, R.Y. and Schmitt-Verhulst, A.M. (1987). Sequential activation and lethal hit measured by [Ca2+)i in individual cytolytic T cells and targets. EMBO J. 6, 2223–2232.
Williams, D.A., Fogarty, K.E., Tsien, R.Y. and Fay, F. (1985). Calcium gradients in single smooth muscle cells revealed by the digital imaging microscope using Fura-2. Nature 318, 558–561.
Wyllie, A.H. (1980). Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284, 555–556.
Young, J.D., Cohn, Z.A. and Podack, E.R. (1986). The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological and functional similarities. Science 233, 184–190.
Zwelling, L.A., Chan, D., Hinds, M., Mayes, J., Silberman, L.E. and Blick, M. (1988). Effect of phorbol ester treatment on drug-induced topoisomerase II-mediated DNA cleavage in human leukemia cells. Cancer Res. 48, 6625–6633.
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© 1991 Plenum Press, New York
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Orrenius, S., McConkey, D.J., Nicotera, P. (1991). Role of Calcium in Toxic and Programmed Cell Death. In: Witmer, C.M., Snyder, R.R., Jollow, D.J., Kalf, G.F., Kocsis, J.J., Sipes, I.G. (eds) Biological Reactive Intermediates IV. Advances in Experimental Medicine and Biology, vol 283. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5877-0_57
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DOI: https://doi.org/10.1007/978-1-4684-5877-0_57
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