Cooper C E, Brown G C
Department of Paediatrics, University College London Medical School, Rayne Institute, UK.
Biochem Biophys Res Commun. 1995 Jul 17;212(2):404-12. doi: 10.1006/bbrc.1995.1984.
It has been proposed that nitric oxide (NO) toxicity is due to damage to mitochondrial iron-sulfur centers, resulting in inhibition of mitochondrial respiration and the appearance of an EPR-detectable (g = 2.04) iron-sulfur dinitrosyl complex - Fe(RS)2(NO)2. We show that the addition of nitroprusside (an NO and NO+ donor) to rat brain synaptosomes generates large (> 30 microM) concentrations of EPR-detectable iron-sulfur-dinitrosyl complexes. However, there was no correlation between the size of the g = 2.04 EPR signal and the inhibition of synaptosomal respiration. No significant loss of intensity was seen from the mitochondrial iron-sulfur protein EPR signals. The results are consistent with previous data demonstrating that cytochrome oxidase, not iron-sulfur enzymes, is the primary target for NO inhibition of brain cell respiration (Brown, G.C. and Cooper, C.E. (1994) FEBS Lett. 356, 295-298).
