Decoding S-nitrosylation: Theoretical aspects and analytical approaches

Since the initial identification of nitric oxide (NO) as an inducer of vasodilation and muscle relaxation in the last few decades, interest in the manifold physiological roles of NO has been rising exponentially. Supporting published evidences are fueling the idea that NO is an enzymatically regulated molecule that is supported by the finding of different NO synthases (NOSs) and denitrosylases responsible for the regulation of NO signaling. This finding extends the way beyond the guanylyl cyclase-adenosine monophosphate (sGC-cAMP) axis. In this report, we review the current status of NO-mediated signaling pathways and S-nitrosation (or S-nitrosylation) of proteins driven via trans-nitrosylation and the mechanisms of denitrosylation, the various roles of NO in physiology and pathology (including vasodilation and muscle cell contraction, neurotransmission, metabolism and bioenergetics, and particularly the role of NO in both innate and adaptive immunities). We also review the various roles of NO in tumorigenesis (including mutagenicity and genome instability, various modes of cell death, angiogenesis, and epithelial-to-mesenchymal transition [EMT]). We review the various methods that have been used for the detection of S-nitrosylated molecules (such as indirect assays [the biotin-switch assay] and direct methods [the SNO-RAC method, gold nanoparticles, organomercury resin capture, organophosphine-based SNO labeling, mass spectrometry, and immunohistochemistry]). The continually evolving landscape of the biologically important mechanisms of S-nitrosylation and denitrosylation offers new therapeutic opportunities for various diseases including cancer.