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Oxygen radicals induce poly(ADP-ribose) polymerase-dependent cell death in cytotoxic lymphocytes

Journal article
Authors Fredrik Bergh Thorén
Ana Romero
Kristoffer Hellstrand
Published in J Immunol
Volume 176
Issue 12
Pages 7301-7
ISSN 0022-1767 (Print)
Publication year 2006
Published at Institute of Biomedicine, Department of Infectious Medicine
Pages 7301-7
Language en
Keywords Apoptosis Inducing Factor/metabolism, Cell Death/drug effects/immunology, Cell Nucleus/metabolism, Free Radicals/metabolism, Humans, Hydrogen Peroxide/pharmacology, Killer Cells, Natural/ cytology/ enzymology/immunology/metabolism, Macrophages/enzymology/metabolism, Phenanthrenes/pharmacology, Poly(ADP-ribose) Polymerases/antagonists & inhibitors/ physiology, Reactive Oxygen Species/ metabolism, T-Lymphocytes, Cytotoxic/ cytology/ enzymology/immunology/metabolism
Subject categories Medical and Health Sciences


Cytotoxic T cells and NK cells will acquire features of apoptosis when exposed to oxygen radicals, but the molecular mechanisms underlying this phenomenon are incompletely understood. We have investigated the role of two enzyme systems responsible for execution of cell death, caspases and the poly(ADP-ribose) polymerase (PARP). We report that although human cytotoxic lymphocytes were only marginally protected by caspase inhibitors, PARP inhibitors completely protected lymphocytes from radical-induced apoptosis and restored their cytotoxic function. The radical-induced, PARP-dependent cell death was accompanied by nuclear accumulation of apoptosis-inducing factor and a characteristic pattern of large-fragment DNA degradation. It is concluded that the PARP/apoptosis-inducing factor axis is critically involved in oxygen radical-induced apoptosis in cytotoxic lymphocytes.

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