Role of thiols in the targeting of S-nitroso thiols to red blood cells

Abstract
We compared the nitric oxide (.NO)-releasing characteristics of two NO donors, the S-nitroso adduct of bovine serum albumin (BSANO) and the S-nitroso adduct of L-glutathione (GSNO). In oxygenated phosphate buffer (pH 7.4) and in hemoglobin solution, both NO donors released .NO only in the presence of a low molecular weight thiol (the most active was L-cysteine). The requirement of thiol to release .NO strongly suggests that a transnitrosation reaction occurs between the S-nitroso adduct of the NO donor and the sulfhydryl group of the NO acceptor. The reaction produced a labile S-nitroso-L-cysteine intermediate that released .NO. As shown by spin-trapping experiments, the transnitrosation reaction involved the formation of .NO (trapped by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide) and .S radicals (trapped by 5,5'-dimethyl-1-pyrroline N-oxide) of both the NO donors and the NO acceptor (L-cysteine). The reaction leading to .S radical formation was distinct from the transnitrosation reaction, since it was oxygen-dependent. We suggest that .S radicals are formed from oxidizing species produced after a reaction between .NO and molecular oxygen (.NO2 is a likely candidate). As for pure .NO gas, the major oxidation product of NO donors, in phosphate buffer (pH 7.4), was NO2-, with no formation of NO3-. In the presence of oxyhemoglobin, both NO donors produced only NO3-. BSANO and GSNO showed distinct patterns of .NO release both in phosphate buffer and in the presence of hemoglobin.(ABSTRACT TRUNCATED AT 250 WORDS)