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The Journal of Immunology, Vol 132, Issue 1 38-42, Copyright © 1984 by American Association of Immunologists

ARTICLES

Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death

JJ Cohen and RC Duke

Dexamethasone and corticosterone kill mouse thymocytes, as measured by eosin uptake, after several hours of in vitro incubation. This killing requires RNA and protein synthesis, because it is inhibited by cycloheximide, emetine, or actinomycin D. An earlier event than cell death is the extensive fragmentation of nuclear DNA into oligonucleosomal subunits; this fragmentation also requires RNA and protein synthesis. The DNA cleavage results from the action of an endonuclease that preferentially cleaves DNA in the linker regions between nucleosomes. This endonuclease is found constitutively in the nuclei of thymocytes and some other cells, and requires calcium and magnesium ions for its activation; if isolated fresh thymocyte nuclei are incubated with these ions, as much as 77% of their DNA is cleaved within 90 min. Thus, the protein for which synthesis is necessary for glucocorticoid-induced thymocyte death is not the endonuclease itself, but is in some way involved in its activation; we suggest that it may be part of a system for transporting calcium into the nucleus. The endonuclease is inhibited by zinc, which also prevents thymocyte death. It appears that glucocorticoids cause thymocyte death by activating an enzyme that rapidly and extensively degrades DNA. This "death from within" is biochemically and morphologically different from toxic or accidental cell death, such as that induced by azide, heat, or antibody and complement treatment. Although mature T cells also contain the endogenous endonuclease, they lack the glucocorticoid-inducible mechanism for activating it, and are thus glucocorticoid-resistant.


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 Toxicol Ind HealthHome page
A. Vojdani, M. Ghoneum, and P. Choppa
Minimizing Cancer Risk Using Molecular Techniques: a Review
Toxicology and Industrial Health, September 1, 1997; 13(5): 589 - 626.
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D. K. Perry, M. J. Smyth, H. R. Stennicke, G. S. Salvesen, P. Duriez, G. G. Poirier, and Y. A. Hannun
Zinc Is a Potent Inhibitor of the Apoptotic Protease, Caspase-3. A NOVEL TARGET FOR ZINC IN THE INHIBITION OF APOPTOSIS
J. Biol. Chem., July 25, 1997; 272(30): 18530 - 18533.
[Abstract] [Full Text] [PDF]

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 Arch DermatolHome page
S. Inachi, H. Mizutani, and M. Shimizu
Epidermal Apoptotic Cell Death in Erythema Multiforme and Stevens-Johnson Syndrome: Contribution of Perforin-Positive Cell Infiltration
Arch Dermatol, July 1, 1997; 133(7): 845 - 849.
[Abstract] [PDF]

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 JEMHome page
S. H. Jeon, M. G. Kang, Y. H. Kim, Y. H. Jin, C. Lee, H.-Y. Chung, H. Kwon, S. D. Park, and R. H. Seong
A New Mouse Gene, SRG3, Related to the SWI3 of Saccharomyces cerevisiae, Is Required for Apoptosis Induced by Glucocorticoids in a Thymoma Cell Line
J. Exp. Med., May 19, 1997; 185(10): 1827 - 1836.
[Abstract] [Full Text] [PDF]

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 BloodHome page
E. Ayroldi, G. Migliorati, L. Cannarile, R. Moraca, D. V. Delfino, and C. Riccardi
CD2 Rescues T Cells From T-Cell Receptor/CD3 Apoptosis: A Role for the Fas/Fas-L System
Blood, May 15, 1997; 89(10): 3717 - 3726.
[Abstract] [Full Text] [PDF]

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V. N. Ivanov and V. N. Ivanov
Transcription Factor Activation during Signal-induced Apoptosis of Immature CD4+CD8+ Thymocytes. A PROTECTIVE ROLE OF c-Fos
J. Biol. Chem., March 28, 1997; 272(13): 8558 - 8566.
[Abstract] [Full Text] [PDF]

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J. W. Montague, F. M. Hughes Jr., and J. A. Cidlowski
Native Recombinant Cyclophilins A, B, and C Degrade DNA Independently of Peptidylprolyl cis-trans-Isomerase Activity. POTENTIAL ROLES OF CYCLOPHILINS IN APOPTOSIS
J. Biol. Chem., March 7, 1997; 272(10): 6677 - 6684.
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Y. Yaoita and K. Nakajima
Induction of Apoptosis and CPP32 Expression by Thyroid Hormone in a Myoblastic Cell Line Derived from Tadpole Tail
J. Biol. Chem., February 21, 1997; 272(8): 5122 - 5127.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
N. B. E. Oldenburg, R. B. Evans-Storms, and J. A. Cidlowski
In Vivo Resistance to Glucocorticoid-Induced Apoptosis in Rat Thymocytes with Normal Steroid Receptor Function in Vitro
Endocrinology, February 1, 1997; 138(2): 810 - 818.
[Abstract] [Full Text] [PDF]

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D. Thomaidou, M. C. Mione, J. F. R. Cavanagh, and J. G. Parnavelas
Apoptosis and Its Relation to the Cell Cycle in the Developing Cerebral Cortex
J. Neurosci., February 1, 1997; 17(3): 1075 - 1085.
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 DevelopmentHome page
N Core, S Bel, S. Gaunt, M Aurrand-Lions, J Pearce, A Fisher, and M Djabali
Altered cellular proliferation and mesoderm patterning in Polycomb-M33-deficient mice
Development, January 2, 1997; 124(3): 721 - 729.
[Abstract] [PDF]

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 PerfusionHome page
S. K Alpard, R. A Vertrees, Weike Tao, D. J Deyo, R. L Brunston JR, and J. B Zwischenberger
Therapeutic hyperthermia
Perfusion, November 1, 1996; 11(6): 425 - 435.
[PDF]

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J. E. Reynolds and A. Eastman
Intracellular Calcium Stores Are Not Required for Bcl-2-mediated Protection from Apoptosis
J. Biol. Chem., November 1, 1996; 271(44): 27739 - 27743.
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DavidJ. McConkey and D. J. McConkey
Calcium-dependent, Interleukin 1beta -converting Enzyme Inhibitor-insensitive Degradation of Lamin B1 and DNA Fragmentation in Isolated Thymocyte Nuclei
J. Biol. Chem., September 13, 1996; 271(37): 22398 - 22406.
[Abstract] [Full Text] [PDF]

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 Arch Otolaryngol Head Neck SurgHome page
K. B. Briskin, C. Fady, M. Wang, and A. Lichtenstein
Apoptotic Inhibition of Head and Neck Squamous Cell Carcinoma Cells by Tumor Necrosis Factor {alpha}
Arch Otolaryngol Head Neck Surg, May 1, 1996; 122(5): 559 - 563.
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M. Hugunin, L. J. Quintal, J. A. Mankovich, and T. Ghayur
Protease Activity of in Vitro Transcribed and Translated Caenorhabditis elegans Cell Death Gene (ced-3) Product
J. Biol. Chem., February 16, 1996; 271(7): 3517 - 3522.
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M. Fraser, S. Tynan, A Papaioannou, C. Ireland, and S. Pittman
Endo-exonuclease of human leukaemic cells: evidence for a role in apoptosis
J. Cell Sci., January 9, 1996; 109(9): 2343 - 2360.
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M. A. Lagarkova, O. V. Iarovaia, and S. V. Razin
Large-scale Fragmentation of Mammalian DNA in the Course of Apoptosis Proceeds via Excision of Chromosomal DNA Loops and Their Oligomers
J. Biol. Chem., September 1, 1995; 270(35): 20239 - 20241.
[Abstract] [Full Text] [PDF]

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 Toxicol PatholHome page
M. Md. Hossain, H. Nakayama, and N. Goto
Apoptosis in the Central Nervous System of Developing Mouse Fetuses from 5-Azacytidine-Administered Dams
Toxicol Pathol, May 1, 1995; 23(3): 367 - 372.
[Abstract] [PDF]

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 ScienceHome page
K Kuida, J. Lippke, G Ku, M. Harding, D. Livingston, M. Su, and R. Flavell
Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme
Science, March 31, 1995; 267(5206): 2000 - 2003.
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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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 ScienceHome page
H Steller
Mechanisms and genes of cellular suicide
Science, March 10, 1995; 267(5203): 1445 - 1449.
[Abstract] [PDF]

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 Toxicol PatholHome page
M. A. Davis, M. W. Smith, S. H. Chang, and B. F. Trump
Characterization of a Renal Epithelial Cell Model of Apoptosis Using Okadaic Acid and the NRK-52E Cell Line
Toxicol Pathol, November 1, 1994; 22(6): 595 - 605.
[Abstract] [PDF]

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 Arch SurgHome page
P. A. Abello, S. A. Fidler, G. B. Bulkley, and T. G. Buchman
Antioxidants Modulate Induction of Programmed Endothelial Cell Death (Apoptosis) by Endotoxin
Arch Surg, February 1, 1994; 129(2): 134 - 141.
[Abstract] [PDF]

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S Cornillon, C Foa, J Davoust, N Buonavista, J. Gross, and P Golstein
Programmed cell death in Dictyostelium
J. Cell Sci., January 10, 1994; 107(10): 2691 - 2704.
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G. Bicknell, R. Snowden, and G. Cohen
Formation of high molecular mass DNA fragments is a marker of apoptosis in the human leukaemic cell line, U937
J. Cell Sci., January 9, 1994; 107(9): 2483 - 2489.
[Abstract] [PDF]

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G. Kulkarni and C. McCulloch
Serum deprivation induces apoptotic cell death in a subset of Balb/c 3T3 fibroblasts
J. Cell Sci., January 5, 1994; 107(5): 1169 - 1179.
[Abstract] [PDF]

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V Garcia-Martinez, D Macias, Y Ganan, J. Garcia-Lobo, M. Francia, M. Fernandez-Teran, and J. Hurle
Internucleosomal DNA fragmentation and programmed cell death (apoptosis) in the interdigital tissue of the embryonic chick leg bud
J. Cell Sci., January 9, 1993; 106(1): 201 - 208.
[Abstract] [PDF]

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F Oberhammer, G Fritsch, M Schmied, M Pavelka, D Printz, T Purchio, H Lassmann, and R Schulte-Hermann
Condensation of the chromatin at the membrane of an apoptotic nucleus is not associated with activation of an endonuclease
J. Cell Sci., January 2, 1993; 104(2): 317 - 326.
[Abstract] [PDF]

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 ScienceHome page
I Garcia, I Martinou, Y Tsujimoto, and J. Martinou
Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene
Science, October 9, 1992; 258(5080): 302 - 304.
[Abstract] [PDF]


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