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eNOS S-nitrosylation in erectile function

International Journal of Impotence Research volume 31, pages 52–53 (2019)Cite this article

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Nitric oxide (NO) signaling through S-nitrosylation has emerged as an important mechanism for post-translational regulation of proteins. Reversible protein S-nitrosylation represents soluble guanylyl cyclase/cyclic guanosine monophosphate (cGMP)-independent NO signaling. It is accomplished by a covalent addition of an NO group to a reactive free thiol of proteins to form S-nitrosothiols (SNOs). Once formed, nitrosothiols can be transferred to free thiols on cysteine residues of proteins via transnitrosation reactions [1]. Transnitrosation allows transfers of NO signaling to a site distant from the NO source. The most abundant endogenous SNO and the major stable intracellular NO reservoir and NO transporter is S-nitrosoglutathione (GSNO), generated by S-nitrosylation of the key antioxidant glutathione (GSH). S-nitrosylation/denitrosylation depends on activities of nitric oxide synthases (NOSs) and denitrosylases. S-nitrosoglutathione reductase (GSNOR) is the enzyme that selectively metabolizes GSNO, and thereby depletes the levels of S-nitrosylated proteins, which are in equilibrium with GSNO [2]. The role of S-nitrosylation in mediating penile erection is, however, not well understood. The findings reported in this issue of the International Journal of Impotence Research in the article entitled “S-Nitrosylation of Endothelial Nitric Oxide Synthase Impacts Erectile Function” [3] offer additional support for S-nitrosylation operating in the penis possibly as a regulator of erectile function.

The authors performed experiments combining molecular and physiologic approaches to evaluate the role of S-nitrosylation in erectile function, suggesting it may serve as an alternative pathway leading to detumescence. Co-localization of eNOS and GSNOR in the mouse and human cavernosal tissue, presented in this study, confirms previous findings in the rodent [4, 5] and elevates these findings to human level. To assess the role of global S-nitrosylation, and specifically eNOS S-nitrosylation, in erectile function, the authors used the GSNOR−/− mouse, and intracavernosal injection of a cell permeable glutathione analog glutathione ethyl ester, respectively. Global S-nitrosylation in GSNOR−/− mice resulted in the inability of these mice to maintain elevated intracavernosal pressure (ICP), while decreased eNOS S-nitrosylation resulted in improved tumescence, suggesting that this post-translational protein modification limited normal erectile function. These findings importantly add to previous reports of the presence of S-nitrosylated eNOS in the penis and the role of S-transnitrosylation in the homeostatic eNOS function of the penis [4, 5].

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Authors and Affiliations

  1. The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA

    Biljana Musicki & Arthur L. Burnett

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  1. Biljana Musicki
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  2. Arthur L. Burnett
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Correspondence to Biljana Musicki.

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Musicki, B., Burnett, A.L. eNOS S-nitrosylation in erectile function. Int J Impot Res 31, 52–53 (2019). https://doi.org/10.1038/s41443-018-0069-8

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