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

• 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.

Nyckelord

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

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