Online citations, reference lists, and bibliographies.
← Back to Search

Glucocorticoids Activate A Suicide Process In Thymocytes Through An Elevation Of Cytosolic Ca2+ Concentration.

D. McConkey, P. Nicotera, P. Hartzell, G. Bellomo, A. Wyllie, S. Orrenius
Published 1989 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Glucocorticoid hormones kill immature thymocytes through the induction of a suicide process commonly referred to as "apoptosis." A characteristic marker for this process is the stimulation of endogenous endonuclease activity which results in the extensive cleavage of cell chromatin. In an attempt to characterize the biochemical events involved in this process, we studied the role of Ca2+ in glucocorticoid-induced DNA fragmentation and cell killing in thymocytes. Treatment of thymocytes from immature rats with the synthetic glucocorticoid methylprednisolone resulted in extensive DNA fragmentation which was preceded by an early, sustained increase in cytosolic Ca2+ concentration. This increase in Ca2+ level was blocked by cycloheximide and actinomycin D, inhibitors of de novo protein and mRNA synthesis, respectively. Prevention of the Ca2+ increase by buffering cytosolic Ca2+ with quin-2, or through incubation of the thymocytes in a "Ca2+-free" medium, prevented endonuclease activation and cell killing. Inhibitors of calmodulin also prevented DNA fragmentation without inhibiting the glucocorticoid-stimulated elevation of cytosolic Ca2+ concentration. The Ca2+ increase appeared to be due to the action of a heat-labile cytosolic factor, synthesized in response to glucocorticoids, which facilitated the influx of extracellular Ca2+. Our findings suggest that glucocorticoids induce thymocyte suicide through an elevation of cytosolic Ca2+ concentration resulting in endonuclease activation, DNA fragmentation, and cell death.
This paper references
Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death.
J. Cohen (1984)
Differences in target cell DNA fragmentation induced by mouse cytotoxic T lymphocytes and natural killer cells.
R. C. Duke (1986)
T-cell differentiation in the rabbit. II. Con A and PHA response of thymus, spleen and lymph node cells and of thymus subpopulations; influence of dexamethasone treatment.
P. Roholl (1983)
Induction of natural killer effectors from human thymus with recombinant IL-2.
J. Michoń (1988)
Precursors of T cell growth factor producing cells in the thymus: ontogeny, frequency, and quantitative recovery in a subpopulation of phenotypically mature thymocytes defined by monoclonal antibody GK-1.5
R. Ceredig (1983)
Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product
C. Weinberger (1985)
Studies on the calcium dependence of human NK cell killing.
J. Ng (1987)
Steroid receptor regulated transcription of specific genes and gene networks.
K. Yamamoto (1985)
A new generation of Ca2+ indicators with greatly improved fluorescence properties.
G. Grynkiewicz (1985)
Endogenous nuclease. Properties and effects on transcribed genes in chromatin.
J. Vanderbilt (1982)
Calcium, dexamethasone, and the antiglucocorticoid RU-486 differentially regulate neuropeptide synthesis in a rat C cell line.
F. Zeytin (1987)
A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid.
Kenneth Burton (1956)
Multiple mechanisms of lymphocyte-mediated killing.
J. Young (1988)
Calcium ion concentrations and DNA fragmentation in target cell destruction by murine cloned cytotoxic T lymphocytes
N. Allbritton (1988)
Transcription factors as oncogenes
T. Pawson (1987)
Cytotoxic T lymphocytes and glucocorticoids activate an endogenous suicide process in target cells
D. Ucker (1987)
Stimulation of endogenous endonuclease activity in hepatocytes exposed to oxidative stress.
D. McConkey (1988)
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
A. Wyllie (1980)
Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesis
A. Wyllie (1984)
Calmodulin and calmodulin-binding proteins in liver cell nuclei.
O. Bachs (1987)
Cytotoxic T lymphocyte mediated lysis without release of serine esterase
H. Ostergaard (1987)
Calcium fluxes and calcium buffering in human neutrophils.
V. von Tscharner (1986)
Cystamine induces toxicity in hepatocytes through the elevation of cytosolic Ca2+ and the stimulation of a nonlysosomal proteolytic system.
P. Nicotera (1986)
Separate glucocorticoid, heavy metal, and heat shock domains in thymic lymphocytes.
E. Maytin (1983)
R 24571: a new powerful inhibitor of red blood cell Ca++-transport ATPase and of calmodulin-regulated functions.
K. Gietzen (1981)
Independence of the lethal actions of glucocorticoids on lymphoid cells from possible hormone effects on calcium uptake.
M. Nicholson (1979)

This paper is referenced by
Apoptosis-the story so far...
Afshin Samali (2005)
Alteration in calcium content and Ca2+-ATPase activity in the liver nuclei of rats orally administered carbon tetrachloride
T. Katsumata (2004)
Pharmacological manipulation of granulocyte apoptosis: potential therapeutic targets.
C. Ward (1999)
Specific and rapid induction of the proapoptotic protein Hrk after growth factor withdrawal in hematopoietic progenitor cells.
C. Sanz (2000)
Gene Regulation in Melanoma Metastasis
M. Bar-Eli (2002)
Post-translational and therapy-induced modifications in rheumatoid arthritis
D. Makrygiannakis (2008)
A biochemical hallmark of apoptosis: Internucleosomal degradation of the genome
M. M. Compton (2004)
The Actions of Steroid Hormones on Animal Cells in Culture: Mechanisms and Applications
P. Darbre (1994)
The apoptosis endonucleases: cleaning up after cell death?
M. Peitsch (1994)
P2x purinoceptor is not important in thymocyte apoptosis.
S. Jiang (1996)
Lymphocyte Apoptosis: Mediation by Increased Type 3 Inositol 1,4,5-Trisphosphate Receptor
A. Khan (1996)
CeReS-18, a novel cell surface sialoglycopeptide, induces cell cycle arrest and apoptosis in a calcium-sensitive manner
N. Betz (2004)
J. Kaszuba-Zwoińska (2017)
The Role of Apoptosis in Development, Tissue Homeostasis and Malignancy
M. Raff (1995)
Cell Death in Oral Tissues and Diseases
Tohru Kaku (1997)
Regulation of gene expression in melanoma: New approaches for treatment
M. C. Leslie (2005)
Apoptosis and necrosis in toxicology: a continuum or distinct modes of cell death?
M. Raffray (1997)
The role of calcium in apoptosis
Joachim Krebs (2004)
Cytosolic Ca2+ Signal Is Involved in Regulating UV-Induced Apoptosis in HeLa Cells
Y. Pu (2001)
Calcium Is a Key Signaling Molecule in β-Lapachone-mediated Cell Death*
C. Tagliarino (2001)
Investigation into the intracellular mechanisms whereby long-chain fatty acids protect the heart in ischaemia/reperfusion
A. Engelbrecht (2005)
Effect of histone H1 on the cytosolic calcium levels in human breast cancer MCF 7 cells.
Vani Ganapathy (2005)
Hormone Regulation of Adult Hippocampal Neurogenesis in the Mammalian Brain
C. Barha (2009)
Role of calcium in glucocorticosteroid-induced apoptosis of thymocytes and lymphoma cells: resurrection of old theories by new findings.
C. Distelhorst (1998)
Cell Death by Apoptosis: Morphological, Genetic and Biochemical Features and Toxicological Implications
G. Palladini (1995)
Is Apoptosis Involved in Glutamate Neurotoxicity
J. Ikeda (1997)
Inhibition of Glucocorticoid-induced Apoptosis by Targeting the Major Splice Variants of BIM mRNA with Small Interfering RNA and Short Hairpin RNA*
M. Abrams (2004)
Mechanism of cell death: Early morphological changes and DNA degradation of apoptosis in rat thymocytes.
X. Sun (1994)
The mechanisms by which pardaxin, a natural cationic antimicrobial peptide, targets the endoplasmic reticulum and induces c-FOS.
Chen-Hung Ting (2014)
Roles of cytoplasmic Ca2+ and intracellular Ca2+ stores in induction and suppression of apoptosis in S49 cells.
X. Bian (1997)
Apoptosis Induced by Gliotoxin Is Preceded by Phosphorylation of Histone H3 and Enhanced Sensitivity of Chromatin to Nuclease Digestion*
P. Waring (1997)
Apoptosis driven by IP3‐linked mitochondrial calcium signals
G. Szalai (1999)
See more
Semantic Scholar Logo Some data provided by SemanticScholar