Contrasting effects of NO and peroxynitrites on HSP70 expression and apoptosis in human monocytes
- Adrie, Christophe Medical Intensive Care Unit, Cochin Port-Royal Hospital, Paris, France;
- Richter, Christoph Institute of Biochemistry, Swiss Federal Institute of Technology, Zurich, Switzerland; and
- Bachelet, Maria Laboratory of Respiratory Physiology, Unité de Formation et de Recherche Cochin Port-Royal, Paris V University, and
- Banzet, Nathalie Laboratory of Respiratory Physiology, Unité de Formation et de Recherche Cochin Port-Royal, Paris V University, and
- François, Dominique Laboratory of Respiratory Physiology, Unité de Formation et de Recherche Cochin Port-Royal, Paris V University, and
- Dinh-Xuan, A. Tuan Laboratory of Respiratory Physiology, Unité de Formation et de Recherche Cochin Port-Royal, Paris V University, and
- Dhainaut, Jean François Medical Intensive Care Unit, Cochin Port-Royal Hospital, Paris, France;
- Polla, Barbara S. Laboratory of Respiratory Physiology, Unité de Formation et de Recherche Cochin Port-Royal, Paris V University, and
- Richard, Marie-Jeanne Laboratory of Biology of Oxidative Stress, Biochemistry C, A. Michallon Hospital, Grenoble, France
Published in:
- American Journal of Physiology-Cell Physiology. - American Physiological Society. - 2000, vol. 279, no. 2, p. C452-C460
English
The free radicals nitric oxide (·NO) and superoxide (O2 − ·) react to form peroxynitrite (ONOO− ), a highly toxic oxidant species. In this study we investigated the respective effects of NO and ONOO− in monocytes from healthy human donors. Purified monocytes were incubated for 6 or 16 h with a pure NO donor ( S-nitroso- N-acetyl-dl-penicillamine, 0–2 mM), an ·NO/ONOO− donor (3-morpholinosydnonimine chlorhydrate, 0–2 mM) with and without superoxide dismutase (200 IU/ml), or pure ONOO− . We provide evidence that 3-morpholinosydnonimine chlorhydrate alone represents a strong stress to human monocytes leading to a dose-dependent increase in heat shock protein-70 (HSP70) expression, mitochondrial membrane depolarization, and cell death by apoptosis and necrosis. These phenomena were abolished by superoxide dismutase, suggesting that ONOO− , but not ·NO, was responsible for the observed effects. This observation was further strengthened by the absence of a stress response in cells exposed to S-nitroso- N-acetyl-dl-penicillamine. Conversely, exposure of cells to ONOO− alone also induced mitochondrial membrane depolarization and cell death by apoptosis and necrosis. Thus ONOO− formation may well explain the toxic effect generally attributed to ·NO.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1152/ajpcell.2000.279.2.c452
- ISSN 0363-6143
- Persistent URL
- https://sonar.ch/global/documents/231566
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