Calcium signaling and cytotoxicity (original) (raw)

Abstract

The divalent calcium cation Ca(2+) is used as a major signaling molecule during cell signal transduction to regulate energy output, cellular metabolism, and phenotype. The basis to the signaling role of Ca(2+) is an intricate network of cellular channels and transporters that allow a low resting concentration of Ca(2+) in the cytosol of the cell ([Ca(2+)]i) but that are also coupled to major dynamic and rapidly exchanging stores. This enables extracellular signals from hormones and growth factors to be transduced as [Ca(2+)]i spikes that are amplitude and frequency encoded. There is considerable evidence that a number of toxic environmental chemicals target these Ca(2+) signaling processes, alter them, and induce cell death by apoptosis. Two major pathways for apoptosis will be considered. The first one involves Ca(2+)-mediated expression of ligands that bind to and activate death receptors such as CD95 (Fas, APO-1). In the second pathway, Ca(2+) has a direct toxic effect and its primary targets include the mitochondria and the endoplasmic reticulum (ER). Mitochondria may respond to an apoptotic Ca(2+) signal by the selective release of cytochrome c or through enhanced production of reactive oxygen species and opening of an inner mitochondrial membrane pore. Toxic agents such as the environmental pollutant tributyltin or the natural plant product thapsigargin, which deplete the ER Ca(2+) stores, will induce as a direct result of this effect the opening of plasma membrane Ca(2+) channels and an ER stress response. In contrast, under some conditions, Ca(2+) signals may be cytoprotective and antagonize the apoptotic machinery.

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Selected References

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  1. Aoki T., Koike T., Nakano T., Shibahara K., Kondo S., Kikuchi H., Honjo T. Induction of Bip mRNA upon programmed cell death of differentiated PC12 cells as well as rat sympathetic neurons. J Biochem. 1997 Jan;121(1):122–127. doi: 10.1093/oxfordjournals.jbchem.a021554. [DOI] [PubMed] [Google Scholar]
  2. Arends M. J., Wyllie A. H. Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol. 1991;32:223–254. doi: 10.1016/b978-0-12-364932-4.50010-1. [DOI] [PubMed] [Google Scholar]
  3. Aw T. Y., Nicotera P., Manzo L., Orrenius S. Tributyltin stimulates apoptosis in rat thymocytes. Arch Biochem Biophys. 1990 Nov 15;283(1):46–50. doi: 10.1016/0003-9861(90)90610-b. [DOI] [PubMed] [Google Scholar]
  4. Baffy G., Miyashita T., Williamson J. R., Reed J. C. 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. 1993 Mar 25;268(9):6511–6519. [PubMed] [Google Scholar]
  5. Bernardi P., Petronilli V. The permeability transition pore as a mitochondrial calcium release channel: a critical appraisal. J Bioenerg Biomembr. 1996 Apr;28(2):131–138. doi: 10.1007/BF02110643. [DOI] [PubMed] [Google Scholar]
  6. Berridge M. J. Elementary and global aspects of calcium signalling. J Physiol. 1997 Mar 1;499(Pt 2):291–306. doi: 10.1113/jphysiol.1997.sp021927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Beutner G., Rück A., Riede B., Brdiczka D. Complexes between hexokinase, mitochondrial porin and adenylate translocator in brain: regulation of hexokinase, oxidative phosphorylation and permeability transition pore. Biochem Soc Trans. 1997 Feb;25(1):151–157. doi: 10.1042/bst0250151. [DOI] [PubMed] [Google Scholar]
  8. Bonfoco E., Krainc D., Ankarcrona M., Nicotera P., Lipton S. A. Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7162–7166. doi: 10.1073/pnas.92.16.7162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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. 1998 Jan 2;17(1):37–49. doi: 10.1093/emboj/17.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brini M., Marsault R., Bastianutto C., Pozzan T., Rizzuto R. Nuclear targeting of aequorin. A new approach for measuring nuclear Ca2+ concentration in intact cells. Cell Calcium. 1994 Oct;16(4):259–268. doi: 10.1016/0143-4160(94)90089-2. [DOI] [PubMed] [Google Scholar]
  11. Báthori G., Szabó I., Schmehl I., Tombola F., Messina A., De Pinto V., Zoratti M. Novel aspects of the electrophysiology of mitochondrial porin. Biochem Biophys Res Commun. 1998 Feb 4;243(1):258–263. doi: 10.1006/bbrc.1997.7926. [DOI] [PubMed] [Google Scholar]
  12. Cai J., Jones D. P. Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss. J Biol Chem. 1998 May 8;273(19):11401–11404. doi: 10.1074/jbc.273.19.11401. [DOI] [PubMed] [Google Scholar]
  13. Cao X., Zhou Y., Lee A. S. Requirement of tyrosine- and serine/threonine kinases in the transcriptional activation of the mammalian grp78/BiP promoter by thapsigargin. J Biol Chem. 1995 Jan 6;270(1):494–502. doi: 10.1074/jbc.270.1.494. [DOI] [PubMed] [Google Scholar]
  14. Carafoli E., Garcia-Martin E., Guerini D. The plasma membrane calcium pump: recent developments and future perspectives. Experientia. 1996 Dec 15;52(12):1091–1100. doi: 10.1007/BF01952107. [DOI] [PubMed] [Google Scholar]
  15. Carafoli E. Intracellular calcium homeostasis. Annu Rev Biochem. 1987;56:395–433. doi: 10.1146/annurev.bi.56.070187.002143. [DOI] [PubMed] [Google Scholar]
  16. Chen S. J., Bradley M. E., Lee T. C. Chemical hypoxia triggers apoptosis of cultured neonatal rat cardiac myocytes: modulation by calcium-regulated proteases and protein kinases. Mol Cell Biochem. 1998 Jan;178(1-2):141–149. doi: 10.1023/a:1006893528428. [DOI] [PubMed] [Google Scholar]
  17. Chen Y. C., Kuo T. C., Lin-Shiau S. Y., Lin J. K. Induction of HSP70 gene expression by modulation of Ca(+2) ion and cellular p53 protein by curcumin in colorectal carcinoma cells. Mol Carcinog. 1996 Dec;17(4):224–234. doi: 10.1002/(SICI)1098-2744(199612)17:4<224::AID-MC6>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
  18. Chow S. C., Kass G. E., McCabe M. J., Jr, Orrenius S. Tributyltin increases cytosolic free Ca2+ concentration in thymocytes by mobilizing intracellular Ca2+, activating a Ca2+ entry pathway, and inhibiting Ca2+ efflux. Arch Biochem Biophys. 1992 Oct;298(1):143–149. doi: 10.1016/0003-9861(92)90105-6. [DOI] [PubMed] [Google Scholar]
  19. Clapham D. E. Calcium signaling. Cell. 1995 Jan 27;80(2):259–268. doi: 10.1016/0092-8674(95)90408-5. [DOI] [PubMed] [Google Scholar]
  20. Cohen G. M. Caspases: the executioners of apoptosis. Biochem J. 1997 Aug 15;326(Pt 1):1–16. doi: 10.1042/bj3260001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Cohen J. J., Duke R. C. Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. J Immunol. 1984 Jan;132(1):38–42. [PubMed] [Google Scholar]
  22. Cohen O., Feinstein E., Kimchi A. DAP-kinase is a Ca2+/calmodulin-dependent, cytoskeletal-associated protein kinase, with cell death-inducing functions that depend on its catalytic activity. EMBO J. 1997 Mar 3;16(5):998–1008. doi: 10.1093/emboj/16.5.998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Cook N., Dexter T. M., Lord B. I., Cragoe E. J., Jr, Whetton A. D. Identification of a common signal associated with cellular proliferation stimulated by four haemopoietic growth factors in a highly enriched population of granulocyte/macrophage colony-forming cells. EMBO J. 1989 Oct;8(10):2967–2974. doi: 10.1002/j.1460-2075.1989.tb08446.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Cossarizza A., Kalashnikova G., Grassilli E., Chiappelli F., Salvioli S., Capri M., Barbieri D., Troiano L., Monti D., Franceschi C. Mitochondrial modifications during rat thymocyte apoptosis: a study at the single cell level. Exp Cell Res. 1994 Sep;214(1):323–330. doi: 10.1006/excr.1994.1264. [DOI] [PubMed] [Google Scholar]
  25. Czarny M., Sabała P., Ucieklak A., Kaczmarek L., Barańska J. Inhibition of phosphatidylserine synthesis by glutamate, acetylcholine, thapsigargin and ionophore A23187 in glioma C6 cells. Biochem Biophys Res Commun. 1992 Aug 14;186(3):1582–1587. doi: 10.1016/s0006-291x(05)81588-8. [DOI] [PubMed] [Google Scholar]
  26. Deshmukh M., Vasilakos J., Deckwerth T. L., Lampe P. A., Shivers B. D., Johnson E. M., Jr Genetic and metabolic status of NGF-deprived sympathetic neurons saved by an inhibitor of ICE family proteases. J Cell Biol. 1996 Dec;135(5):1341–1354. doi: 10.1083/jcb.135.5.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Dowd D. R., MacDonald P. N., Komm B. S., Haussler M. R., Miesfeld R. L. Stable expression of the calbindin-D28K complementary DNA interferes with the apoptotic pathway in lymphocytes. Mol Endocrinol. 1992 Nov;6(11):1843–1848. doi: 10.1210/mend.6.11.1336124. [DOI] [PubMed] [Google Scholar]
  28. Duddy S. K., Kass G. E., Orrenius S. Ca2(+)-mobilizing hormones stimulate Ca2+ efflux from hepatocytes. J Biol Chem. 1989 Dec 15;264(35):20863–20866. [PubMed] [Google Scholar]
  29. Dypbukt J. M., Ankarcrona M., Burkitt M., Sjöholm A., Ström K., Orrenius S., Nicotera P. Different prooxidant levels stimulate growth, trigger apoptosis, or produce necrosis of insulin-secreting RINm5F cells. The role of intracellular polyamines. J Biol Chem. 1994 Dec 2;269(48):30553–30560. [PubMed] [Google Scholar]
  30. Eibl B., Schwaighofer H., Nachbaur D., Marth C., Gächter A., Knapp R., Böck G., Gassner C., Schiller L., Petersen F. Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer. Blood. 1996 Aug 15;88(4):1501–1508. [PubMed] [Google Scholar]
  31. Felzen B., Shilkrut M., Less H., Sarapov I., Maor G., Coleman R., Robinson R. B., Berke G., Binah O. Fas (CD95/Apo-1)-mediated damage to ventricular myocytes induced by cytotoxic T lymphocytes from perforin-deficient mice: a major role for inositol 1,4,5-trisphosphate. Circ Res. 1998 Mar 9;82(4):438–450. doi: 10.1161/01.res.82.4.438. [DOI] [PubMed] [Google Scholar]
  32. Franklin J. L., Johnson E. M., Jr Elevated intracellular calcium blocks programmed neuronal death. Ann N Y Acad Sci. 1994 Dec 15;747:195–204. doi: 10.1111/j.1749-6632.1994.tb44410.x. [DOI] [PubMed] [Google Scholar]
  33. Froelich C. J., Dixit V. M., Yang X. Lymphocyte granule-mediated apoptosis: matters of viral mimicry and deadly proteases. Immunol Today. 1998 Jan;19(1):30–36. doi: 10.1016/s0167-5699(97)01184-5. [DOI] [PubMed] [Google Scholar]
  34. Ghafourifar P., Richter C. Nitric oxide synthase activity in mitochondria. FEBS Lett. 1997 Dec 1;418(3):291–296. doi: 10.1016/s0014-5793(97)01397-5. [DOI] [PubMed] [Google Scholar]
  35. Ghibelli L., Coppola S., Rotilio G., Lafavia E., Maresca V., Ciriolo M. R. Non-oxidative loss of glutathione in apoptosis via GSH extrusion. Biochem Biophys Res Commun. 1995 Nov 2;216(1):313–320. doi: 10.1006/bbrc.1995.2626. [DOI] [PubMed] [Google Scholar]
  36. Gommerman J. L., Berger S. A. Protection from apoptosis by steel factor but not interleukin-3 is reversed through blockade of calcium influx. Blood. 1998 Mar 15;91(6):1891–1900. [PubMed] [Google Scholar]
  37. Guo Q., Christakos S., Robinson N., Mattson M. P. Calbindin D28k blocks the proapoptotic actions of mutant presenilin 1: reduced oxidative stress and preserved mitochondrial function. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3227–3232. doi: 10.1073/pnas.95.6.3227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Hampton M. B., Zhivotovsky B., Slater A. F., Burgess D. H., Orrenius S. Importance of the redox state of cytochrome c during caspase activation in cytosolic extracts. Biochem J. 1998 Jan 1;329(Pt 1):95–99. doi: 10.1042/bj3290095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. He H., Lam M., McCormick T. S., Distelhorst C. W. Maintenance of calcium homeostasis in the endoplasmic reticulum by Bcl-2. J Cell Biol. 1997 Sep 22;138(6):1219–1228. doi: 10.1083/jcb.138.6.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Henkart P. A. ICE family proteases: mediators of all apoptotic cell death? Immunity. 1996 Mar;4(3):195–201. doi: 10.1016/s1074-7613(00)80428-8. [DOI] [PubMed] [Google Scholar]
  41. Hüser J., Rechenmacher C. E., Blatter L. A. Imaging the permeability pore transition in single mitochondria. Biophys J. 1998 Apr;74(4):2129–2137. doi: 10.1016/S0006-3495(98)77920-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Jacobson M. D., Weil M., Raff M. C. Programmed cell death in animal development. Cell. 1997 Feb 7;88(3):347–354. doi: 10.1016/s0092-8674(00)81873-5. [DOI] [PubMed] [Google Scholar]
  43. Jamora C., Dennert G., Lee A. S. Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7690–7694. doi: 10.1073/pnas.93.15.7690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Jayaraman T., Marks A. R. T cells deficient in inositol 1,4,5-trisphosphate receptor are resistant to apoptosis. Mol Cell Biol. 1997 Jun;17(6):3005–3012. doi: 10.1128/mcb.17.6.3005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Jewell S. A., Bellomo G., Thor H., Orrenius S., Smith M. Bleb formation in hepatocytes during drug metabolism is caused by disturbances in thiol and calcium ion homeostasis. Science. 1982 Sep 24;217(4566):1257–1259. doi: 10.1126/science.7112127. [DOI] [PubMed] [Google Scholar]
  46. Jiang S., Chow S. C., Nicotera P., Orrenius S. Intracellular Ca2+ signals activate apoptosis in thymocytes: studies using the Ca(2+)-ATPase inhibitor thapsigargin. Exp Cell Res. 1994 May;212(1):84–92. doi: 10.1006/excr.1994.1121. [DOI] [PubMed] [Google Scholar]
  47. Johnson R. J., Liu N., Shanmugaratnam J., Fine R. E. Increased calreticulin stability in differentiated NG-108-15 cells correlates with resistance to apoptosis induced by antisense treatment. Brain Res Mol Brain Res. 1998 Jan;53(1-2):104–111. doi: 10.1016/s0169-328x(97)00284-2. [DOI] [PubMed] [Google Scholar]
  48. Jones R. A., Johnson V. L., Buck N. R., Dobrota M., Hinton R. H., Chow S. C., Kass G. E. Fas-mediated apoptosis in mouse hepatocytes involves the processing and activation of caspases. Hepatology. 1998 Jun;27(6):1632–1642. doi: 10.1002/hep.510270624. [DOI] [PubMed] [Google Scholar]
  49. Jordán J., Galindo M. F., Miller R. J. Role of calpain- and interleukin-1 beta converting enzyme-like proteases in the beta-amyloid-induced death of rat hippocampal neurons in culture. J Neurochem. 1997 Apr;68(4):1612–1621. doi: 10.1046/j.1471-4159.1997.68041612.x. [DOI] [PubMed] [Google Scholar]
  50. Juedes M. J., Kass G. E., Orrenius S. m-iodobenzylguanidine increases the mitochondrial Ca2+ pool in isolated hepatocytes. FEBS Lett. 1992 Nov 16;313(1):39–42. doi: 10.1016/0014-5793(92)81179-p. [DOI] [PubMed] [Google Scholar]
  51. Juin P., Pelletier M., Oliver L., Tremblais K., Grégoire M., Meflah K., Vallette F. M. Induction of a caspase-3-like activity by calcium in normal cytosolic extracts triggers nuclear apoptosis in a cell-free system. J Biol Chem. 1998 Jul 10;273(28):17559–17564. doi: 10.1074/jbc.273.28.17559. [DOI] [PubMed] [Google Scholar]
  52. Jürgensmeier J. M., Xie Z., Deveraux Q., Ellerby L., Bredesen D., Reed J. C. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4997–5002. doi: 10.1073/pnas.95.9.4997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Kane D. J., Ord T., Anton R., Bredesen D. E. Expression of bcl-2 inhibits necrotic neural cell death. J Neurosci Res. 1995 Feb 1;40(2):269–275. doi: 10.1002/jnr.490400216. [DOI] [PubMed] [Google Scholar]
  54. Kane D. J., Sarafian T. A., Anton R., Hahn H., Gralla E. B., Valentine J. S., Ord T., Bredesen D. E. Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science. 1993 Nov 19;262(5137):1274–1277. doi: 10.1126/science.8235659. [DOI] [PubMed] [Google Scholar]
  55. Kaneko Y., Tsukamoto A. Thapsigargin-induced persistent intracellular calcium pool depletion and apoptosis in human hepatoma cells. Cancer Lett. 1994 May 16;79(2):147–155. doi: 10.1016/0304-3835(94)90253-4. [DOI] [PubMed] [Google Scholar]
  56. Kantrow S. P., Piantadosi C. A. Release of cytochrome c from liver mitochondria during permeability transition. Biochem Biophys Res Commun. 1997 Mar 27;232(3):669–671. doi: 10.1006/bbrc.1997.6353. [DOI] [PubMed] [Google Scholar]
  57. Kass G. E., Chow S. C., Gahm A., Webb D. L., Berggren P. O., Llopis J., Orrenius S. Two separate plasma membrane Ca2+ carriers participate in receptor-mediated Ca2+ influx in rat hepatocytes. Biochim Biophys Acta. 1994 Sep 8;1223(2):226–233. doi: 10.1016/0167-4889(94)90230-5. [DOI] [PubMed] [Google Scholar]
  58. Kass G. E., Duddy S. K., Moore G. A., Orrenius S. 2,5-Di-(tert-butyl)-1,4-benzohydroquinone rapidly elevates cytosolic Ca2+ concentration by mobilizing the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. J Biol Chem. 1989 Sep 15;264(26):15192–15198. [PubMed] [Google Scholar]
  59. Kass G. E., Eriksson J. E., Weis M., Orrenius S., Chow S. C. Chromatin condensation during apoptosis requires ATP. Biochem J. 1996 Sep 15;318(Pt 3):749–752. doi: 10.1042/bj3180749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Kass G. E., Juedes M. J., Orrenius S. Cyclosporin A protects hepatocytes against prooxidant-induced cell killing. A study on the role of mitochondrial Ca2+ cycling in cytotoxicity. Biochem Pharmacol. 1992 Nov 17;44(10):1995–2003. doi: 10.1016/0006-2952(92)90102-o. [DOI] [PubMed] [Google Scholar]
  61. Kass G. E., Llopis J., Chow S. C., Duddy S. K., Orrenius S. Receptor-operated calcium influx in rat hepatocytes. Identification and characterization using manganese. J Biol Chem. 1990 Oct 15;265(29):17486–17492. [PubMed] [Google Scholar]
  62. Kass G. E., Wright J. M., Nicotera P., Orrenius S. The mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity: role of intracellular calcium. Arch Biochem Biophys. 1988 Feb 1;260(2):789–797. doi: 10.1016/0003-9861(88)90509-7. [DOI] [PubMed] [Google Scholar]
  63. Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Khan A. A., Soloski M. J., Sharp A. H., Schilling G., Sabatini D. M., Li S. H., Ross C. A., Snyder S. H. Lymphocyte apoptosis: mediation by increased type 3 inositol 1,4,5-trisphosphate receptor. Science. 1996 Jul 26;273(5274):503–507. doi: 10.1126/science.273.5274.503. [DOI] [PubMed] [Google Scholar]
  65. Kidd V. J. Proteolytic activities that mediate apoptosis. Annu Rev Physiol. 1998;60:533–573. doi: 10.1146/annurev.physiol.60.1.533. [DOI] [PubMed] [Google Scholar]
  66. Kluck R. M., Bossy-Wetzel E., Green D. R., Newmeyer D. D. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 1997 Feb 21;275(5303):1132–1136. doi: 10.1126/science.275.5303.1132. [DOI] [PubMed] [Google Scholar]
  67. Koike T., Martin D. P., Johnson E. M., Jr Role of Ca2+ channels in the ability of membrane depolarization to prevent neuronal death induced by trophic-factor deprivation: evidence that levels of internal Ca2+ determine nerve growth factor dependence of sympathetic ganglion cells. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6421–6425. doi: 10.1073/pnas.86.16.6421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Kraev A., Chumakov I., Carafoli E. Molecular biological studies of the cardiac sodium-calcium exchanger. Ann N Y Acad Sci. 1996 Apr 15;779:103–109. doi: 10.1111/j.1749-6632.1996.tb44774.x. [DOI] [PubMed] [Google Scholar]
  69. Krippner A., Matsuno-Yagi A., Gottlieb R. A., Babior B. M. Loss of function of cytochrome c in Jurkat cells undergoing fas-mediated apoptosis. J Biol Chem. 1996 Aug 30;271(35):21629–21636. doi: 10.1074/jbc.271.35.21629. [DOI] [PubMed] [Google Scholar]
  70. Kroemer G., Dallaporta B., Resche-Rigon M. The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol. 1998;60:619–642. doi: 10.1146/annurev.physiol.60.1.619. [DOI] [PubMed] [Google Scholar]
  71. Lam M., Dubyak G., Chen L., Nuñez G., Miesfeld R. L., Distelhorst C. W. Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6569–6573. doi: 10.1073/pnas.91.14.6569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Lam M., Dubyak G., Distelhorst C. W. Effect of glucocorticosteroid treatment on intracellular calcium homeostasis in mouse lymphoma cells. Mol Endocrinol. 1993 May;7(5):686–693. doi: 10.1210/mend.7.5.8316252. [DOI] [PubMed] [Google Scholar]
  73. Lampe P. A., Cornbrooks E. B., Juhasz A., Johnson E. M., Jr, Franklin J. L. Suppression of programmed neuronal death by a thapsigargin-induced Ca2+ influx. J Neurobiol. 1995 Feb;26(2):205–212. doi: 10.1002/neu.480260205. [DOI] [PubMed] [Google Scholar]
  74. Leist M., Single B., Castoldi A. F., Kühnle S., Nicotera P. Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med. 1997 Apr 21;185(8):1481–1486. doi: 10.1084/jem.185.8.1481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Lemasters J. J., Nieminen A. L., Qian T., Trost L. C., Herman B. The mitochondrial permeability transition in toxic, hypoxic and reperfusion injury. Mol Cell Biochem. 1997 Sep;174(1-2):159–165. [PubMed] [Google Scholar]
  76. 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. 1998 Aug 21;94(4):491–501. doi: 10.1016/s0092-8674(00)81590-1. [DOI] [PubMed] [Google Scholar]
  77. Li P., Nijhawan D., Budihardjo I., Srinivasula S. M., Ahmad M., Alnemri E. S., Wang X. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997 Nov 14;91(4):479–489. doi: 10.1016/s0092-8674(00)80434-1. [DOI] [PubMed] [Google Scholar]
  78. Li W. W., Hsiung Y., Zhou Y., Roy B., Lee A. S. Induction of the mammalian GRP78/BiP gene by Ca2+ depletion and formation of aberrant proteins: activation of the conserved stress-inducible grp core promoter element by the human nuclear factor YY1. Mol Cell Biol. 1997 Jan;17(1):54–60. doi: 10.1128/mcb.17.1.54. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Lin C., Hajnóczky G., Thomas A. P. Propagation of cytosolic calcium waves into the nuclei of hepatocytes. Cell Calcium. 1994 Oct;16(4):247–258. doi: 10.1016/0143-4160(94)90088-4. [DOI] [PubMed] [Google Scholar]
  80. Liu H., Bowes R. C., 3rd, van de Water B., Sillence C., Nagelkerke J. F., Stevens J. L. Endoplasmic reticulum chaperones GRP78 and calreticulin prevent oxidative stress, Ca2+ disturbances, and cell death in renal epithelial cells. J Biol Chem. 1997 Aug 29;272(35):21751–21759. doi: 10.1074/jbc.272.35.21751. [DOI] [PubMed] [Google Scholar]
  81. Liu H., Miller E., van de Water B., Stevens J. L. Endoplasmic reticulum stress proteins block oxidant-induced Ca2+ increases and cell death. J Biol Chem. 1998 May 22;273(21):12858–12862. doi: 10.1074/jbc.273.21.12858. [DOI] [PubMed] [Google Scholar]
  82. Liu N., Fine R. E., Simons E., Johnson R. J. Decreasing calreticulin expression lowers the Ca2+ response to bradykinin and increases sensitivity to ionomycin in NG-108-15 cells. J Biol Chem. 1994 Nov 18;269(46):28635–28639. [PubMed] [Google Scholar]
  83. Liu X., Kim C. N., Yang J., Jemmerson R., Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 1996 Jul 12;86(1):147–157. doi: 10.1016/s0092-8674(00)80085-9. [DOI] [PubMed] [Google Scholar]
  84. Lièvremont J. P., Rizzuto R., Hendershot L., Meldolesi J. BiP, a major chaperone protein of the endoplasmic reticulum lumen, plays a direct and important role in the storage of the rapidly exchanging pool of Ca2+. J Biol Chem. 1997 Dec 5;272(49):30873–30879. doi: 10.1074/jbc.272.49.30873. [DOI] [PubMed] [Google Scholar]
  85. Llopis J., Chow S. B., Kass G. E., Gahm A., Orrenius S. Comparison between the effects of the microsomal Ca(2+)-translocase inhibitors thapsigargin and 2,5-di-(t-butyl)-1,4-benzohydroquinone on cellular calcium fluxes. Biochem J. 1991 Jul 15;277(Pt 2):553–556. doi: 10.1042/bj2770553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Llopis J., Farrell G. C., Duddy S. K., Kass G. E., Gahm A., Orrenius S. Eicosanoids released following inhibition of the endoplasmic reticulum Ca2+ pump stimulate Ca2+ efflux in the perfused rat liver. Biochem Pharmacol. 1993 Jun 9;45(11):2209–2214. doi: 10.1016/0006-2952(93)90191-x. [DOI] [PubMed] [Google Scholar]
  87. Llopis J., Kass G. E., Gahm A., Orrenius S. Evidence for two pathways of receptor-mediated Ca2+ entry in hepatocytes. Biochem J. 1992 May 15;284(Pt 1):243–247. doi: 10.1042/bj2840243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Long G. J., Pounds J. G., Rosen J. F. Lead intoxication alters basal and parathyroid hormone-regulated cellular calcium homeostasis in rat osteosarcoma (ROS 17/2.8) cells. Calcif Tissue Int. 1992 May;50(5):451–458. doi: 10.1007/BF00296777. [DOI] [PubMed] [Google Scholar]
  89. Lotem J., Sachs L. Different mechanisms for suppression of apoptosis by cytokines and calcium mobilizing compounds. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4601–4606. doi: 10.1073/pnas.95.8.4601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Luo X., Budihardjo I., Zou H., Slaughter C., Wang X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 1998 Aug 21;94(4):481–490. doi: 10.1016/s0092-8674(00)81589-5. [DOI] [PubMed] [Google Scholar]
  91. Majno G., Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol. 1995 Jan;146(1):3–15. [PMC free article] [PubMed] [Google Scholar]
  92. Mariani S. M., Krammer P. H. Surface expression of TRAIL/Apo-2 ligand in activated mouse T and B cells. Eur J Immunol. 1998 May;28(5):1492–1498. doi: 10.1002/(SICI)1521-4141(199805)28:05<1492::AID-IMMU1492>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
  93. Marin M. C., Fernandez A., Bick R. J., Brisbay S., Buja L. M., Snuggs M., McConkey D. J., von Eschenbach A. C., Keating M. J., McDonnell T. J. Apoptosis suppression by bcl-2 is correlated with the regulation of nuclear and cytosolic Ca2+. Oncogene. 1996 Jun 6;12(11):2259–2266. [PubMed] [Google Scholar]
  94. Markovac J., Goldstein G. W. Picomolar concentrations of lead stimulate brain protein kinase C. Nature. 1988 Jul 7;334(6177):71–73. doi: 10.1038/334071a0. [DOI] [PubMed] [Google Scholar]
  95. Marks A. R. Intracellular calcium-release channels: regulators of cell life and death. Am J Physiol. 1997 Feb;272(2 Pt 2):H597–H605. doi: 10.1152/ajpheart.1997.272.2.H597. [DOI] [PubMed] [Google Scholar]
  96. Marzo I., Brenner C., Zamzami N., Susin S. A., Beutner G., Brdiczka D., Rémy R., Xie Z. H., Reed J. C., Kroemer G. The permeability transition pore complex: a target for apoptosis regulation by caspases and bcl-2-related proteins. J Exp Med. 1998 Apr 20;187(8):1261–1271. doi: 10.1084/jem.187.8.1261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. McConkey D. J. Calcium-dependent, interleukin 1-converting enzyme inhibitor-insensitive degradation of lamin B1 and DNA fragmentation in isolated thymocyte nuclei. J Biol Chem. 1996 Sep 13;271(37):22398–22406. doi: 10.1074/jbc.271.37.22398. [DOI] [PubMed] [Google Scholar]
  98. McConkey D. J., Hartzell P., Nicotera P., Orrenius S. Calcium-activated DNA fragmentation kills immature thymocytes. FASEB J. 1989 May;3(7):1843–1849. doi: 10.1096/fasebj.3.7.2497041. [DOI] [PubMed] [Google Scholar]
  99. McConkey D. J., Nicotera P., Hartzell P., Bellomo G., Wyllie A. H., Orrenius S. Glucocorticoids activate a suicide process in thymocytes through an elevation of cytosolic Ca2+ concentration. Arch Biochem Biophys. 1989 Feb 15;269(1):365–370. doi: 10.1016/0003-9861(89)90119-7. [DOI] [PubMed] [Google Scholar]
  100. McCormick T. S., McColl K. S., Distelhorst C. W. Mouse lymphoma cells destined to undergo apoptosis in response to thapsigargin treatment fail to generate a calcium-mediated grp78/grp94 stress response. J Biol Chem. 1997 Feb 28;272(9):6087–6092. doi: 10.1074/jbc.272.9.6087. [DOI] [PubMed] [Google Scholar]
  101. Mkrtchian S., Fang C., Hellman U., Ingelman-Sundberg M. A stress-inducible rat liver endoplasmic reticulum protein, ERp29. Eur J Biochem. 1998 Jan 15;251(1-2):304–313. doi: 10.1046/j.1432-1327.1998.2510304.x. [DOI] [PubMed] [Google Scholar]
  102. Montero M., Brini M., Marsault R., Alvarez J., Sitia R., Pozzan T., Rizzuto R. Monitoring dynamic changes in free Ca2+ concentration in the endoplasmic reticulum of intact cells. EMBO J. 1995 Nov 15;14(22):5467–5475. doi: 10.1002/j.1460-2075.1995.tb00233.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Murphy A. N., Bredesen D. E., Cortopassi G., Wang E., Fiskum G. Bcl-2 potentiates the maximal calcium uptake capacity of neural cell mitochondria. Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9893–9898. doi: 10.1073/pnas.93.18.9893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Muthukkumar S., Nair P., Sells S. F., Maddiwar N. G., Jacob R. J., Rangnekar V. M. Role of EGR-1 in thapsigargin-inducible apoptosis in the melanoma cell line A375-C6. Mol Cell Biol. 1995 Nov;15(11):6262–6272. doi: 10.1128/mcb.15.11.6262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. Nagata S. Apoptosis by death factor. Cell. 1997 Feb 7;88(3):355–365. doi: 10.1016/s0092-8674(00)81874-7. [DOI] [PubMed] [Google Scholar]
  106. Nath R., Raser K. J., Stafford D., Hajimohammadreza I., Posner A., Allen H., Talanian R. V., Yuen P., Gilbertsen R. B., Wang K. K. Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1 beta-converting-enzyme-like protease(s) in apoptotic cells: contributory roles of both protease families in neuronal apoptosis. Biochem J. 1996 Nov 1;319(Pt 3):683–690. doi: 10.1042/bj3190683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. Nicholson D. W., Thornberry N. A. Caspases: killer proteases. Trends Biochem Sci. 1997 Aug;22(8):299–306. doi: 10.1016/s0968-0004(97)01085-2. [DOI] [PubMed] [Google Scholar]
  108. Nicotera P., Hartzell P., Davis G., Orrenius S. The formation of plasma membrane blebs in hepatocytes exposed to agents that increase cytosolic Ca2+ is mediated by the activation of a non-lysosomal proteolytic system. FEBS Lett. 1986 Dec 1;209(1):139–144. doi: 10.1016/0014-5793(86)81099-7. [DOI] [PubMed] [Google Scholar]
  109. Nicotera P., McConkey D. J., Jones D. P., Orrenius S. ATP stimulates Ca2+ uptake and increases the free Ca2+ concentration in isolated rat liver nuclei. Proc Natl Acad Sci U S A. 1989 Jan;86(2):453–457. doi: 10.1073/pnas.86.2.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  110. Nicotera P., Zhivotovsky B., Orrenius S. Nuclear calcium transport and the role of calcium in apoptosis. Cell Calcium. 1994 Oct;16(4):279–288. doi: 10.1016/0143-4160(94)90091-4. [DOI] [PubMed] [Google Scholar]
  111. Oberhammer F., Wilson J. W., Dive C., Morris I. D., Hickman J. A., Wakeling A. E., Walker P. R., Sikorska M. Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation. EMBO J. 1993 Sep;12(9):3679–3684. doi: 10.1002/j.1460-2075.1993.tb06042.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Ogasawara J., Watanabe-Fukunaga R., Adachi M., Matsuzawa A., Kasugai T., Kitamura Y., Itoh N., Suda T., Nagata S. Lethal effect of the anti-Fas antibody in mice. Nature. 1993 Aug 26;364(6440):806–809. doi: 10.1038/364806a0. [DOI] [PubMed] [Google Scholar]
  113. Orrenius S., Burkitt M. J., Kass G. E., Dypbukt J. M., Nicotera P. Calcium ions and oxidative cell injury. Ann Neurol. 1992;32 (Suppl):S33–S42. doi: 10.1002/ana.410320708. [DOI] [PubMed] [Google Scholar]
  114. Orrenius S., Nicotera P. The calcium ion and cell death. J Neural Transm Suppl. 1994;43:1–11. [PubMed] [Google Scholar]
  115. Palaga T., Kataoka T., Woo J. T., Nagai K. Suppression of apoptotic cell death of IL-3-dependent cell lines by ER/SR Ca2+-ATPase inhibitors upon IL-3 deprivation. Exp Cell Res. 1996 Oct 10;228(1):92–97. doi: 10.1006/excr.1996.0303. [DOI] [PubMed] [Google Scholar]
  116. Pan G., Humke E. W., Dixit V. M. Activation of caspases triggered by cytochrome c in vitro. FEBS Lett. 1998 Apr 10;426(1):151–154. doi: 10.1016/s0014-5793(98)00330-5. [DOI] [PubMed] [Google Scholar]
  117. Parekh A. B., Penner R. Store depletion and calcium influx. Physiol Rev. 1997 Oct;77(4):901–930. doi: 10.1152/physrev.1997.77.4.901. [DOI] [PubMed] [Google Scholar]
  118. Pastorino J. G., Chen S. T., Tafani M., Snyder J. W., Farber J. L. The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition. J Biol Chem. 1998 Mar 27;273(13):7770–7775. doi: 10.1074/jbc.273.13.7770. [DOI] [PubMed] [Google Scholar]
  119. Pelassy C., Breittmayer J. P., Aussel C. Agonist-induced inhibition of phosphatidylserine synthesis is secondary to the emptying of intracellular Ca2+ stores in Jurkat T-cells. Biochem J. 1992 Dec 15;288(Pt 3):785–789. doi: 10.1042/bj2880785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  120. Petit P. X., Goubern M., Diolez P., Susin S. A., Zamzami N., Kroemer G. Disruption of the outer mitochondrial membrane as a result of large amplitude swelling: the impact of irreversible permeability transition. FEBS Lett. 1998 Apr 10;426(1):111–116. doi: 10.1016/s0014-5793(98)00318-4. [DOI] [PubMed] [Google Scholar]
  121. Pike B. R., Zhao X., Newcomb J. K., Wang K. K., Posmantur R. M., Hayes R. L. Temporal relationships between de novo protein synthesis, calpain and caspase 3-like protease activation, and DNA fragmentation during apoptosis in septo-hippocampal cultures. J Neurosci Res. 1998 Jun 1;52(5):505–520. doi: 10.1002/(SICI)1097-4547(19980601)52:5<505::AID-JNR3>3.0.CO;2-G. [DOI] [PubMed] [Google Scholar]
  122. Pozzan T., Rizzuto R., Volpe P., Meldolesi J. Molecular and cellular physiology of intracellular calcium stores. Physiol Rev. 1994 Jul;74(3):595–636. doi: 10.1152/physrev.1994.74.3.595. [DOI] [PubMed] [Google Scholar]
  123. Preston G. A., Barrett J. C., Biermann J. A., Murphy E. Effects of alterations in calcium homeostasis on apoptosis during neoplastic progression. Cancer Res. 1997 Feb 1;57(3):537–542. [PubMed] [Google Scholar]
  124. Putney J. W., Jr A model for receptor-regulated calcium entry. Cell Calcium. 1986 Feb;7(1):1–12. doi: 10.1016/0143-4160(86)90026-6. [DOI] [PubMed] [Google Scholar]
  125. Putney J. W., Jr, Bird G. S. The inositol phosphate-calcium signaling system in nonexcitable cells. Endocr Rev. 1993 Oct;14(5):610–631. doi: 10.1210/edrv-14-5-610. [DOI] [PubMed] [Google Scholar]
  126. Qi X. M., He H., Zhong H., Distelhorst C. W. Baculovirus p35 and Z-VAD-fmk inhibit thapsigargin-induced apoptosis of breast cancer cells. Oncogene. 1997 Sep 4;15(10):1207–1212. doi: 10.1038/sj.onc.1201290. [DOI] [PubMed] [Google Scholar]
  127. Raffray M., Cohen G. M. Apoptosis and necrosis in toxicology: a continuum or distinct modes of cell death? Pharmacol Ther. 1997 Sep;75(3):153–177. doi: 10.1016/s0163-7258(97)00037-5. [DOI] [PubMed] [Google Scholar]
  128. Richter C., Kass G. E. Oxidative stress in mitochondria: its relationship to cellular Ca2+ homeostasis, cell death, proliferation, and differentiation. Chem Biol Interact. 1991;77(1):1–23. doi: 10.1016/0009-2797(91)90002-o. [DOI] [PubMed] [Google Scholar]
  129. Rizzuto R., Bastianutto C., Brini M., Murgia M., Pozzan T. Mitochondrial Ca2+ homeostasis in intact cells. J Cell Biol. 1994 Sep;126(5):1183–1194. doi: 10.1083/jcb.126.5.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  130. Rizzuto R., Pinton P., Carrington W., Fay F. S., Fogarty K. E., Lifshitz L. M., Tuft R. A., Pozzan T. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science. 1998 Jun 12;280(5370):1763–1766. doi: 10.1126/science.280.5370.1763. [DOI] [PubMed] [Google Scholar]
  131. Rodriguez-Tarduchy G., Collins M., López-Rivas A. Regulation of apoptosis in interleukin-3-dependent hemopoietic cells by interleukin-3 and calcium ionophores. EMBO J. 1990 Sep;9(9):2997–3002. doi: 10.1002/j.1460-2075.1990.tb07492.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  132. Rossi A. D., Larsson O., Manzo L., Orrenius S., Vahter M., Berggren P. O., Nicotera P. Modifications of Ca2+ signaling by inorganic mercury in PC12 cells. FASEB J. 1993 Dec;7(15):1507–1514. doi: 10.1096/fasebj.7.15.8262335. [DOI] [PubMed] [Google Scholar]
  133. Roy B., Lee A. S. Transduction of calcium stress through interaction of the human transcription factor CBF with the proximal CCAAT regulatory element of the grp78/BiP promoter. Mol Cell Biol. 1995 Apr;15(4):2263–2274. doi: 10.1128/mcb.15.4.2263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  134. Roy B., Li W. W., Lee A. S. Calcium-sensitive transcriptional activation of the proximal CCAAT regulatory element of the grp78/BiP promoter by the human nuclear factor CBF/NF-Y. J Biol Chem. 1996 Nov 15;271(46):28995–29002. doi: 10.1074/jbc.271.46.28995. [DOI] [PubMed] [Google Scholar]
  135. Rudin C. M., Thompson C. B. Apoptosis and disease: regulation and clinical relevance of programmed cell death. Annu Rev Med. 1997;48:267–281. doi: 10.1146/annurev.med.48.1.267. [DOI] [PubMed] [Google Scholar]
  136. Rutter G. A., Burnett P., Rizzuto R., Brini M., Murgia M., Pozzan T., Tavaré J. M., Denton R. M. Subcellular imaging of intramitochondrial Ca2+ with recombinant targeted aequorin: significance for the regulation of pyruvate dehydrogenase activity. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5489–5494. doi: 10.1073/pnas.93.11.5489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  137. Santella L., Carafoli E. Calcium signaling in the cell nucleus. FASEB J. 1997 Nov;11(13):1091–1109. [PubMed] [Google Scholar]
  138. Schulman H., Hanson P. I., Meyer T. Decoding calcium signals by multifunctional CaM kinase. Cell Calcium. 1992 Jun-Jul;13(6-7):401–411. doi: 10.1016/0143-4160(92)90053-u. [DOI] [PubMed] [Google Scholar]
  139. Shibasaki F., Kondo E., Akagi T., McKeon F. Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bcl-2. Nature. 1997 Apr 17;386(6626):728–731. doi: 10.1038/386728a0. [DOI] [PubMed] [Google Scholar]
  140. Shibasaki F., McKeon F. Calcineurin functions in Ca(2+)-activated cell death in mammalian cells. J Cell Biol. 1995 Nov;131(3):735–743. doi: 10.1083/jcb.131.3.735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  141. Shimizu S., Eguchi Y., Kamiike W., Waguri S., Uchiyama Y., Matsuda H., Tsujimoto Y. Retardation of chemical hypoxia-induced necrotic cell death by Bcl-2 and ICE inhibitors: possible involvement of common mediators in apoptotic and necrotic signal transductions. Oncogene. 1996 May 16;12(10):2045–2050. [PubMed] [Google Scholar]
  142. Silver P. A. How proteins enter the nucleus. Cell. 1991 Feb 8;64(3):489–497. doi: 10.1016/0092-8674(91)90233-o. [DOI] [PubMed] [Google Scholar]
  143. Smith J. B., Dwyer S. D., Smith L. Cadmium evokes inositol polyphosphate formation and calcium mobilization. Evidence for a cell surface receptor that cadmium stimulates and zinc antagonizes. J Biol Chem. 1989 May 5;264(13):7115–7118. [PubMed] [Google Scholar]
  144. Smith J. B., Smith L., Pijuan V., Zhuang Y., Chen Y. C. Transmembrane signals and protooncogene induction evoked by carcinogenic metals and prevented by zinc. Environ Health Perspect. 1994 Sep;102 (Suppl 3):181–189. doi: 10.1289/ehp.94102s3181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  145. Soler R. M., Egea J., Mintenig G. M., Sanz-Rodriguez C., Iglesias M., Comella J. X. Calmodulin is involved in membrane depolarization-mediated survival of motoneurons by phosphatidylinositol-3 kinase- and MAPK-independent pathways. J Neurosci. 1998 Feb 15;18(4):1230–1239. doi: 10.1523/JNEUROSCI.18-04-01230.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  146. Squier M. K., Cohen J. J. Calpain, an upstream regulator of thymocyte apoptosis. J Immunol. 1997 Apr 15;158(8):3690–3697. [PubMed] [Google Scholar]
  147. Strasser A., Harris A. W., Cory S. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell. 1991 Nov 29;67(5):889–899. doi: 10.1016/0092-8674(91)90362-3. [DOI] [PubMed] [Google Scholar]
  148. Takadera T., Ohyashiki T. Apoptotic cell death and CPP32-like activation induced by thapsigargin and their prevention by nerve growth factor in PC12 cells. Biochim Biophys Acta. 1998 Jan 2;1401(1):63–71. doi: 10.1016/s0167-4889(97)00116-x. [DOI] [PubMed] [Google Scholar]
  149. Tinton S. A., Chow S. C., Buc-Calderon P. M., Kass G. E. Adenosine stimulates calcium influx in isolated rat hepatocytes. Eur J Biochem. 1996 Jun 1;238(2):576–581. doi: 10.1111/j.1432-1033.1996.0576z.x. [DOI] [PubMed] [Google Scholar]
  150. Tinton S. A., Chow S. C., Buc-Calderon P. M., Kass G. E., Orrenius S. Adenosine inhibits protein synthesis in isolated rat hepatocytes. Evidence for a lack of involvement of intracellular calcium in the mechanism of inhibition. Eur J Biochem. 1995 Apr 15;229(2):419–425. doi: 10.1111/j.1432-1033.1995.0419k.x. [DOI] [PubMed] [Google Scholar]
  151. Trump B. F., Berezesky I. K., Chang S. H., Phelps P. C. The pathways of cell death: oncosis, apoptosis, and necrosis. Toxicol Pathol. 1997 Jan-Feb;25(1):82–88. doi: 10.1177/019262339702500116. [DOI] [PubMed] [Google Scholar]
  152. Trump B. F., Berezesky I. K. The role of altered [Ca2+]i regulation in apoptosis, oncosis, and necrosis. Biochim Biophys Acta. 1996 Oct 11;1313(3):173–178. doi: 10.1016/0167-4889(96)00086-9. [DOI] [PubMed] [Google Scholar]
  153. Tsien R. W., Tsien R. Y. Calcium channels, stores, and oscillations. Annu Rev Cell Biol. 1990;6:715–760. doi: 10.1146/annurev.cb.06.110190.003435. [DOI] [PubMed] [Google Scholar]
  154. Tsujimoto Y. Apoptosis and necrosis: intracellular ATP level as a determinant for cell death modes. Cell Death Differ. 1997 Aug;4(6):429–434. doi: 10.1038/sj.cdd.4400262. [DOI] [PubMed] [Google Scholar]
  155. Vanags D. M., Pörn-Ares M. I., Coppola S., Burgess D. H., Orrenius S. Protease involvement in fodrin cleavage and phosphatidylserine exposure in apoptosis. J Biol Chem. 1996 Dec 6;271(49):31075–31085. doi: 10.1074/jbc.271.49.31075. [DOI] [PubMed] [Google Scholar]
  156. Villa P., Kaufmann S. H., Earnshaw W. C. Caspases and caspase inhibitors. Trends Biochem Sci. 1997 Oct;22(10):388–393. doi: 10.1016/s0968-0004(97)01107-9. [DOI] [PubMed] [Google Scholar]
  157. Viviani B., Rossi A. D., Chow S. C., Nicotera P. Organotin compounds induce calcium overload and apoptosis in PC12 cells. Neurotoxicology. 1995 Spring;16(1):19–25. [PubMed] [Google Scholar]
  158. Waring P., Beaver J. Cyclosporin A rescues thymocytes from apoptosis induced by very low concentrations of thapsigargin: effects on mitochondrial function. Exp Cell Res. 1996 Sep 15;227(2):264–276. doi: 10.1006/excr.1996.0276. [DOI] [PubMed] [Google Scholar]
  159. Waring P., Sjaarda A. Extracellular calcium is not required for gliotoxin or dexamethasone-induced DNA fragmentation: a reappraisal of the use of EGTA. Int J Immunopharmacol. 1995 May;17(5):403–410. doi: 10.1016/0192-0561(95)00021-s. [DOI] [PubMed] [Google Scholar]
  160. Weis M., Kass G. E., Orrenius S. Further characterization of the events involved in mitochondrial Ca2+ release and pore formation by prooxidants. Biochem Pharmacol. 1994 Jun 15;47(12):2147–2156. doi: 10.1016/0006-2952(94)90249-6. [DOI] [PubMed] [Google Scholar]
  161. Weis M., Schlegel J., Kass G. E., Holmström T. H., Peters I., Eriksson J., Orrenius S., Chow S. C. Cellular events in Fas/APO-1-mediated apoptosis in JURKAT T lymphocytes. Exp Cell Res. 1995 Aug;219(2):699–708. doi: 10.1006/excr.1995.1281. [DOI] [PubMed] [Google Scholar]
  162. Whyte M. K., Hardwick S. J., Meagher L. C., Savill J. S., Haslett C. Transient elevations of cytosolic free calcium retard subsequent apoptosis in neutrophils in vitro. J Clin Invest. 1993 Jul;92(1):446–455. doi: 10.1172/JCI116587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  163. Wong W. L., Brostrom M. A., Kuznetsov G., Gmitter-Yellen D., Brostrom C. O. Inhibition of protein synthesis and early protein processing by thapsigargin in cultured cells. Biochem J. 1993 Jan 1;289(Pt 1):71–79. doi: 10.1042/bj2890071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  164. Wright S. C., Schellenberger U., Ji L., Wang H., Larrick J. W. Calmodulin-dependent protein kinase II mediates signal transduction in apoptosis. FASEB J. 1997 Sep;11(11):843–849. doi: 10.1096/fasebj.11.11.9285482. [DOI] [PubMed] [Google Scholar]
  165. Wright S. C., Schellenberger U., Wang H., Kinder D. H., Talhouk J. W., Larrick J. W. Activation of CPP32-like proteases is not sufficient to trigger apoptosis: inhibition of apoptosis by agents that suppress activation of AP24, but not CPP32-like activity. J Exp Med. 1997 Oct 6;186(7):1107–1117. doi: 10.1084/jem.186.7.1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  166. Wyllie A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980 Apr 10;284(5756):555–556. doi: 10.1038/284555a0. [DOI] [PubMed] [Google Scholar]
  167. Wyllie A. H., Morris R. G., Smith A. L., Dunlop D. Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol. 1984 Jan;142(1):67–77. doi: 10.1002/path.1711420112. [DOI] [PubMed] [Google Scholar]
  168. Yang J., Liu X., Bhalla K., Kim C. N., Ibrado A. M., Cai J., Peng T. I., Jones D. P., Wang X. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997 Feb 21;275(5303):1129–1132. doi: 10.1126/science.275.5303.1129. [DOI] [PubMed] [Google Scholar]
  169. Zhivotovsky B., Orrenius S., Brustugun O. T., Døskeland S. O. Injected cytochrome c induces apoptosis. Nature. 1998 Jan 29;391(6666):449–450. doi: 10.1038/35060. [DOI] [PubMed] [Google Scholar]
  170. Zhu H., Fearnhead H. O., Cohen G. M. An ICE-like protease is a common mediator of apoptosis induced by diverse stimuli in human monocytic THP.1 cells. FEBS Lett. 1995 Oct 30;374(2):303–308. doi: 10.1016/0014-5793(95)01116-v. [DOI] [PubMed] [Google Scholar]
  171. Zoratti M., Szabò I. The mitochondrial permeability transition. Biochim Biophys Acta. 1995 Jul 17;1241(2):139–176. doi: 10.1016/0304-4157(95)00003-a. [DOI] [PubMed] [Google Scholar]
  172. van den Dobbelsteen D. J., Nobel C. S., Schlegel J., Cotgreave I. A., Orrenius S., Slater A. F. Rapid and specific efflux of reduced glutathione during apoptosis induced by anti-Fas/APO-1 antibody. J Biol Chem. 1996 Jun 28;271(26):15420–15427. doi: 10.1074/jbc.271.26.15420. [DOI] [PubMed] [Google Scholar]