Iron catalyzes both decomposition and synthesis of S-nitrosothiols: Optical and electron paramagnetic resonance studies

Formation of S-nitrosothiols was demonstrated in 1-50 mM aqueous solutions of cysteine or glutathione (cys-NO or OS-NO, respectively) upon contact of thiols with gaseous nitric oxide under a pressure of 50-600 mm Hg and anaerobic conditions. The yield of S-nitrosothhiols was increased by mixing with NO plus air at a molar ratio [NO]/[O-2 from air] of no less than 40. In this instance, the S-nitrosothiol formation was optimum at a NO pressure of 100-150 mm Hg. The addition of 0.25 mM o-phenanthroline, a selective Fe2+ chelator, to thiol solutions prior to the treatment with NO or NO + air completely blocked the formation of S-nitrosothiols. On the other hand, this process was potentiated by the addition of Fe2+ but not Cu2+ ions, These data indicated a crucial influence of Fe2+ on the process. The contact of o-phenanthroline with S-nitrosothiols synthesized by a routine method (treatment of thiol solutions with the NO + NO2 mixture at pH <1) did not induce their degradation at pH 3-10, Moreover, o-phenanthroline strikingly enhanced the cys-NO stability at neutral pH, Cysteine, glutathione, and desferal, a selective Fe3+ chelator, exerted a similar effect on cys-NO, The stabilizing effect of thiols on cys-NO was accompanied by the formation of dinitrosyl-iron complexes with thiol-containing ligands containing admired (intrinsic) iron (1-2 mu M) The addition of Fe2+ at a concentration higher than 10 mu l abolished the stabilizing effect of thiols on cys-NO. Therefore iron can induce both degradation and synthesis of S-nitrosothiols, According to the proposed mechanisms such opposite effects of iron on S-nitrosothiols are determined by the ratio between S-nitrosothiols, thiols, iron, and NO in the reaction system. (C) 1997 Academic Press.