Key result
Endogenous and exogenous nitric oxide regulate protein S-nitrosylation, a reversible posttranslational modification that dynamically impacts protein interactions, function, and vascular tone.
Why the study?
Inhaled nitric oxide is an established therapy for pulmonary hypertension in neonates and has been proposed for hypoxic respiratory failure and ARDS due to COVID-19, motivating a review of endogenous and exogenous NO effects on protein S-nitrosylation.
This review highlights the complex biological consequences of protein S-nitrosylation by endogenous and inhaled nitric oxide, emphasizing its role in both physiological autoregulation and pathological enzyme inhibition.
S-nitrosylation by endogenous/exogenous NO may modulate vascular tone; leaves open targeted therapeutic modulation in pulmonary vascular disease.
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 in neonates, and has been recently proposed for the 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 posttranslational 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 nonenzymatic 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.
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Bhatia et al. (2020) conducted a review in Protein S-nitrosylation. Nitric oxide was evaluated. Endogenous and exogenous nitric oxide regulate protein S-nitrosylation, a reversible posttranslational modification that dynamically impacts protein interactions, function, and vascular tone.
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