“…Similarly, about a hundred proteins are capable of S-(de)nitrosylation, another highly stringent post-translational redox modification within the intracellular milieu, where both the S-nitrosylated as well as denitrosylated proteins are responsible for cellular NO-signaling. Very few protein-SNOs are stable or are not denitrosylated in physiological GSH concentrations; these proteins include caspase-3, α-tubulin, β-tubulin, collapsin response mediator protein-2, Creatine kinase (B chain), extracellular signal-regulated kinase-2, glutathione-S-transferase (GST) pi, glyceraldehyde-3-phosphate dehydrogenase (GADPH), hemoglobin (β chain), pyruvate kinase, and Prx6 [ 29 , 55 , 56 , 57 ]. Amongst all these protein-SNOs, the most prominent is caspase-3, which cannot be denitrosylated by GSH or GSNOR, but exclusively by Trx; this proves the S-nitrosylation of this apoptotic protein by NO donors, but the failure of the activity regeneration in the absence of Trx, which again establishes a link between caspases and cancer and eliminates the direct role of GSH in the same, while indirectly GSH as well as reduced human Trxs have the potential to denitrosylated S-nitroso thioredoxins, inactivating caspase-3, linking GSH to the apoptotic pathways [ 12 , 58 ].…”