Differential induction of apoptosis in Swiss 3T3 cells by nitric oxide and the nitrosonium cation.

Abstract:

:We have investigated the effect of nitric oxide (NO) on apoptosis in Swiss 3T3 fibroblasts and compared it to the effect of the nitrosonium cation (NO+). Both species induced apoptosis, confirmed by electron microscopy, propidium iodide staining, DNA laddering and activation of caspases. The kinetics of triggering apoptosis were different for the two redox species: NO+ required only a 2 hour exposure, whereas NO required 24 hours. Three sources of NO were used: aqueous solutions of NO and two NO donors, S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine. The time course of apoptosis induced by these two S-nitrosothiols correlated with their rate of decomposition to NO. The apoptotic effect of NO was reduced in the presence of the NO scavenger oxyhaemoglobin, or the antioxidants N-acetylcysteine and ascorbic acid, whereas in the case of NO+ these antioxidants potentiated apoptosis. Glutathione also had a potentiating effect on the cytotoxicity of NO+. This suggests that cellular antioxidants may play a role in protecting the cell from NO-induced apoptosis while NO+ may trigger apoptosis independently of oxidative stress mechanisms.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Khan S,Kayahara M,Joashi U,Mazarakis ND,Sarraf C,Edwards AD,Hughes MN,Mehmet H

subject

Has Abstract

pub_date

1997-09-01 00:00:00

pages

2315-22

eissn

0021-9533

issn

1477-9137

journal_volume

110 ( Pt 18)

pub_type

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