Key result
Inhaled and endogenous nitric oxide regulate vascular and airway tone through protein S-nitrosylation, which dynamically impacts protein interactions, hypoxic vasodilation, and vasodilator enzymes.
Why the study?
Inhaled nitric oxide is an established and proposed therapy, but the physiological and pathological biological consequences of endogenous and exogenous nitric oxide on protein S-nitrosylation warranted a comprehensive review.
This review highlights the complex biological consequences of protein S-nitrosylation by nitric oxide, emphasizing the balance between physiological vasodilation and pathological enzyme inhibition.
Cautions against untargeted NO therapies due to enzyme effects; leaves open clinical translation of S-nitrosylation modulation.
Nitric oxide (NO) is a comprehensive regulator of vascular and airway tone. Endogenous NO produced by nitric oxide synthases regulates multiple signaling cascades, including activation of soluble guanylate cyclase to generate cGMP, relaxing smooth muscle cells. Inhaled NO is an established therapy for pulmonary hypertension, especially in neonates, and has been recently proposed for treatment of hypoxic respiratory failure and acute respiratory distress syndrome due to COVID-19. In this review, we summarize the effects of endogenous and exogenous NO on protein S-nitrosylation, which is the selective and reversible covalent attachment of a nitrogen monoxide group to the thiol side chain of cysteine. This post-translational modification targets specific cysteines based on the acid/base sequence of surrounding residues, with significant impacts on protein interactions and function. S-nitrosothiol (SNO) formation is tightly compartmentalized and enzymatically controlled, but also propagated by non-enzymatic transnitrosylation of downstream protein targets. Redox-based nitrosylation and denitrosylation pathways dynamically regulate the equilibrium of SNO-proteins. We review the physiological roles of SNO proteins, including nitrosohemoglobin and autoregulation of blood flow through hypoxic vasodilation, and pathological effects of nitrosylation including inhibition of critical vasodilator enzymes; and discuss the intersection of NO source and dose with redox environment, in determining the effects of protein nitrosylation.
No takes yet. Share an insight, caveat, or question.
Bhatia et al. (2020) conducted a review in Pulmonary hypertension, hypoxic respiratory failure, acute respiratory distress syndrome. Inhaled Nitric Oxide was evaluated. Inhaled and endogenous nitric oxide regulate vascular and airway tone through protein S-nitrosylation, which dynamically impacts protein interactions, hypoxic vasodilation, and vasodilator enzymes.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: