Regulation of S-thiolation and S-nitrosylation in the thiol/nitric oxide system by radical scavengers.
Nitric oxide (NO) is a possible agent, which induces crosslinking among molecules containing sulfhydryl groups. However, the S-thiolation is essentially accompanied by S-nitrosylation. In the present study, we evaluated radical scavengers as a regulator for S-thiolation and S-nitrosylation by NO released from NO-generator, 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (P-NONOate). When glutathione was incubated with P-NONOate in 4% (vol/vol) O(2)-saturated buffer solution (pH 7.4) in the presence of nitrone spin-trapping agent, 5,5'-dimethyl-1-pyroline-N-oxide (DMPO), the prevention of S-thiolation and the promotion of S-nitrosylation were observed. The DMPO adduct was identified to be thiyl radical-DMPO adduct via ESR study. In contrast, nitroxyl radical, radical scavenger against oxygen-centered radicals, promoted the S-thiolation but prevented S-nitrosylation. Nitronyl nitroxide, radical scavenger against nitric oxide, can convert nitric oxide into nitrogen dioxide in the O(2)-independent manner. In the presence of nitronyl nitroxide in the thiol/P-NONOate system, S-thiolation was remarkably enhanced up to 60% (mol/mol) of sulfhydryl groups. However, nitronyl nitroxide at enough content (>or=1.0 mM) almost completely prevented S-nitrosylation, whereas nitronyl nitroxide at comparatively lower content (0.5 mM) contrarily enhanced the S-nitrosylation. Based on these facts, it appeared to be possible to consequently regulate S-thiolation and S-nitrosylation through controlling the thiyl radical chain reaction by radical scavengers.
Koshiishi
Ichiro
I
Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kita-Adachi-gun, Saitama 362-0806, Japan. ikoshi@nichiyaku.ac.jp
Takajo
Tokuko
T
Tsuchida
Kazunori
K
D000975:Antioxidants / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry*; D009603:Nitroso Compounds / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D013113:Spin Labels; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013455:Sulfur / Q000737:chemistry*; D014226:Triazenes / Q000737:chemistry
D000975:Antioxidants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D009603:Nitroso Compounds; D013113:Spin Labels; D013438:Sulfhydryl Compounds; D014226:Triazenes; D009569:Nitric Oxide; D013455:Sulfur; D005978:Glutathione; D010100:Oxygen