title: 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.
authors.affiliation: Department of Chemistry, King's College London, Strand, London WC2R 2LS, UK.
authors.forename: S
authors.initials: S
authors.lastname: Khan
authors.forename: M
authors.initials: M
authors.lastname: Kayahara
authors.forename: U
authors.initials: U
authors.lastname: Joashi
authors.forename: N D
authors.initials: ND
authors.lastname: Mazarakis
authors.forename: C
authors.initials: C
authors.lastname: Sarraf
authors.forename: A D
authors.initials: AD
authors.lastname: Edwards
authors.forename: M N
authors.initials: MN
authors.lastname: Hughes
authors.forename: H
authors.initials: H
authors.lastname: Mehmet
mesh_terms: D016475:3T3 Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002412:Cations / Q000378:metabolism*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D026422:S-Nitrosoglutathione; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D013997:Time Factors; D033921:Vesicular Transport Proteins
chemical_list: D000931:Antidotes; D000975:Antioxidants; D002352:Carrier Proteins; D002412:Cations; D016166:Free Radical Scavengers; D008565:Membrane Proteins; D009603:Nitroso Compounds; D010108:Oxyhemoglobins; D010975:Platelet Aggregation Inhibitors; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D011065:Poly(ADP-ribose) Polymerases; D005978:Glutathione; D001205:Ascorbic Acid; D000111:Acetylcysteine