In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 279, No. 2 ( 2000-08-01), p. C452-C460
Abstract:
The free radicals nitric oxide (·NO) and superoxide (O 2 − ·) 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.
Type of Medium:
Online Resource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.2000.279.2.C452
Language:
English
Publisher:
American Physiological Society
Publication Date:
2000
detail.hit.zdb_id:
1477334-X
SSG:
12
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