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PMID: 9154798 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

T cells deficient in inositol 1,4,5-trisphosphate receptor are resistant to apoptosis.

Molecular and cellular biology ·Vol. 17 ·No. 6 ·1997-06-00 ·Pages 3005-12

Jayaraman T, Marks AR

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.

MeSH Terms
Apoptosis Calcium/metabolism Calcium Channels/deficiency Chelating Agents/pharmacology Egtazic Acid/pharmacology Enzyme Inhibitors/pharmacology Humans Inositol 1,4,5-Trisphosphate/metabolism Inositol 1,4,5-Trisphosphate Receptors Jurkat Cells Receptors, Antigen, T-Cell/metabolism Receptors, Cytoplasmic and Nuclear/deficiency Signal Transduction T-Lymphocytes/chemistry,physiology Thapsigargin/pharmacology fas Receptor/metabolism
Chemicals
Calcium Channels Chelating Agents Enzyme Inhibitors ITPR1 protein, human Inositol 1,4,5-Trisphosphate Receptors Receptors, Antigen, T-Cell Receptors, Cytoplasmic and Nuclear fas Receptor Egtazic Acid Thapsigargin Inositol 1,4,5-Trisphosphate Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Jayaraman T
Molecular Cardiology Program, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Marks A R
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.17.6.3005
Published
1997-06-00
Pages
3005-12
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC232152
Subset
IM
Grants
NHLBI NIH HHS · HL56180 · United States
NIAID NIH HHS · R01 AI39794 · United States
External Links
PubMed source DOI: 10.1128/MCB.17.6.3005 PMC Full Text View journal details
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