PMID:17580965

Citation	Sengupta, R, Ryter, SW, Zuckerbraun, BS, Tzeng, E, Billiar, TR and Stoyanovsky, DA (2007) Thioredoxin catalyzes the denitrosation of low-molecular mass and protein S-nitrosothiols. Biochemistry 46:8472-83
Abstract	While most proteins have critical thiols whose oxidation affects their activity, it has been suggested that S-nitrosation and denitrosation of cellular thiols are fundamental processes similar to protein phosphorylation and dephosphorylation, respectively. However, understanding the biosynthesis and catabolism of S-nitrosothiols has proven to be difficult, in part because of the low stability of this class of metabolites. Herein, we report that thioredoxin catalyzes the denitrosation of a series of S-nitrosoamino acids and S-nitrosoproteins derived from HepG2 cells. Notably, all S-nitrosoproteins with a molecular mass of 23-30 kDa were catabolized by thioredoxin. Experimental evidence is presented which shows that both glutathione and reduced human thioredoxin denitrosate S-nitrosothioredoxin, which has been suggested to act as an anti-apoptotic factor via trans-S-nitrosation of caspase 3. In HepG2 cells, we observed that S-nitrosocysteine ethyl ester impedes the activity of caspase 3. However, a subsequent incubation of the cells in nitrosothiol-free medium resulted in reconstitution of the enzymatic activity, most likely due to endogenous denitrosation of S-nitrosocaspase 3. The latter process was markedly inhibited in thioredoxin reductase-deficient HepG2 cells, suggesting that the thioredoxin/thioredoxin reductase system tends to maintain intracellular caspase 3 in a reduced, SH state. The data obtained are discussed within the general reaction mechanisms encompassing the cellular homeostasis of S-nitrosothiols.
Links	PubMed Online version:10.1021/bi700449x
Keywords	Amino Acids/chemistry; Amino Acids/metabolism; Caspase 3/metabolism; Catalysis; Cell Line, Tumor; Glutathione/metabolism; Humans; Mitochondrial Proteins/metabolism; Molecular Weight; Nitrosation; Proteins/chemistry; Proteins/metabolism; S-Nitrosothiols/metabolism; Thioredoxin-Disulfide Reductase/metabolism; Thioredoxins/chemistry; Thioredoxins/metabolism
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