Affiliation:
1. Molecular Cardiology Program, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Abstract
The type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) calcium release channel is present on the endoplasmic reticulum of most cell types. T lymphocytes which have been made deficient in IP3R1 lack detectable IP3-induced intracellular calcium release and exhibit defective signaling via the T-cell receptor (TCR) (T. Jayaraman, E. Ondriasova, K. Ondrias, D. Harnick, and A. R. Marks, Proc. Natl. Acad. Sci. USA 92:6007-6011, 1995). We now show that IP3R1-deficient T cells are resistant to apoptosis induced by dexamethasone, TCR stimulation, ionizing radiation, and Fas. Resistance to TCR-mediated apoptosis in IP3R1-deficient cells is reversed by pharmacologically raising cytoplasmic calcium levels. TCR-mediated apoptosis can be induced in calcium-free media, indicating that extracellular calcium influx is not required. These findings suggest that intracellular calcium release via the IP3R1 is a critical mediator of apoptosis.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference60 articles.
1. Up-regulated expression of Fas antigen (CD95) by peripheral naive and memory T cell subsets in patients with systemic Iupus erythematosus (SLE): a possible mechanism for lymphopenia;Amasaki Y.;Clin. Exp. Immunol.,1995
2. The effect of the immunosuppressant FK506 on alternate pathways of T cell activation;Bierer B. E.;Eur. J. Immunol.,1991
3. p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes;Caelles C.;Nature,1994
4. Glucocorticoid activation of a calciumdependent endonuclease in thymocyte nuclei leads to cell death;Cohen J. J.;J. Immunol.,1984
5. Coligan J. E. A. M. Kruisbeek D. H. Margulies E. M. Shevach and W. Strober (ed.). 1990. Current protocols in immunology vol. 1. Wiley Interscience New York N.Y.
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