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The Journal of Immunology, Vol 145, Issue 6 1859-1867, Copyright © 1990 by American Association of Immunologists
ARTICLES |
SJ Martin, SV Lennon, AM Bonham and TG Cotter
Department of Biology, St. Patrick's College, Maynooth, County Kildare, Republic of Ireland.
Apoptosis is regarded as a suicidal cell response since the dying cell appears to be an active participant. Previous studies have shown that apoptosis of various murine cell types, induced by a variety of stimuli, required RNA and/or protein synthesis. However, when human promyelocytic leukemia HL-60 cells were induced to undergo apoptosis by treatment with the calcium ionophore A23187 or microtubule-disrupting agents, in the presence of inhibitors of macromolecular synthesis, apoptosis of these cells was neither abrogated nor delayed. Furthermore, the presence of either cycloheximide, an inhibitor of protein synthesis, or actinomycin D, an RNA synthesis inhibitor, alone was found to induce large scale apoptosis of these cells. Apoptosis in these cells was characterized by cell and chromatin condensation followed by nuclear and DNA fragmentation. In common with many other studies, this DNA fragmentation was found to have an approximately 200- bp multiple pattern, which is consistent with the activation of an endogenous endonuclease which cleaves at internucleosomal sites. Calcium-dependent endonuclease activity of this type was also detected in the isolated nuclei of untreated HL-60 cells. The morphologic and biochemical changes characteristic of apoptosis were found to precede cell death, as measured by trypan blue uptake and were completely distinct from death caused by toxic stimuli such as azide, ethanol, or heat treatment. Similar experiments with six other human cell lines confirmed that this phenomenon was not peculiar to the HL-60 cell line. These results suggest that certain dividing cell populations do not require RNA or protein synthesis to undergo apoptosis and further, that continuous transcription and translation of some regulatory protein(s) may be required to maintain control over the apoptotic "machinery" of such cells.
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A. J. Polverino and S. D. Patterson Selective Activation of Caspases During Apoptotic Induction in HL-60 Cells. EFFECTS OF A TETRAPEPTIDE INHIBITOR J. Biol. Chem., March 14, 1997; 272(11): 7013 - 7021. [Abstract] [Full Text] [PDF]
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Z. Han, N. Malik, T. Carter, W. H. Reeves, J. H. Wyche, and E. A. Hendrickson DNA-dependent Protein Kinase Is a Target for a CPP32-like Apoptotic Protease J. Biol. Chem., October 4, 1996; 271(40): 25035 - 25040. [Abstract] [Full Text] [PDF]
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D. Pérez-Sala, D. Collado-Escobar, and F. Mollinedo Intracellular Alkalinization Suppresses Lovastatin-induced Apoptosis in HL-60 Cells through the Inactivation of a pH-dependent Endonuclease J. Biol. Chem., March 17, 1995; 270(11): 6235 - 6242. [Abstract] [Full Text] [PDF]
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