Protein S-nitrosylation in Health and Disease: a Current Perspective

Overview

Journal Trends Mol Med

Specialties General Medicine
Molecular Biology

Date 2009 Sep 4

PMID 19726230

Citations 343

Authors

Matthew W Foster

Douglas T Hess

Jonathan S Stamler

Affiliations

Soon will be listed here.

Abstract

Protein S-nitrosylation constitutes a large part of the ubiquitous influence of nitric oxide on cellular signal transduction and accumulating evidence indicates important roles for S-nitrosylation both in normal physiology and in a broad spectrum of human diseases. Here we review recent findings that implicate S-nitrosylation in cardiovascular, pulmonary, musculoskeletal and neurological (dys)function, as well as in cancer. The emerging picture shows that, in many cases, pathophysiology correlates with hypo- or hyper-S-nitrosylation of specific protein targets rather than a general cellular insult due to loss of or enhanced nitric oxide synthase activity. In addition, it is increasingly evident that dysregulated S-nitrosylation can not only result from alterations in the expression, compartmentalization and/or activity of nitric oxide synthases, but can also reflect a contribution from denitrosylases, including prominently the S-nitrosoglutathione (GSNO)-metabolizing enzyme GSNO reductase. Finally, because exogenous mediators of protein S-nitrosylation or denitrosylation can substantially affect the development or progression of disease, potential therapeutic agents that modulate S-nitrosylation could well have broad clinical utility.

Citing Articles

Multifunctionality and Possible Medical Application of the BPC 157 Peptide-Literature and Patent Review.

Jozwiak M, Bauer M, Kamysz W, Kleczkowska P Pharmaceuticals (Basel). 2025; 18(2).

PMID: 40005999 PMC: 11859134. DOI: 10.3390/ph18020185.

Islet NO-Synthases, extracellular NO and glucose-stimulated insulin secretion: Possible impact of neuronal NO-Synthase on the pentose phosphate pathway.

Lundquist I, Mohammed Al-Amily I, Henningsson R, Salehi A PLoS One. 2025; 20(1):e0315126.

PMID: 39854399 PMC: 11760571. DOI: 10.1371/journal.pone.0315126.

Regulation and Pharmacology of the Cyclic GMP and Nitric Oxide Pathway in Embryonic and Adult Stem Cells.

Kots A, Bian K Cells. 2024; 13(23).

PMID: 39682756 PMC: 11639989. DOI: 10.3390/cells13232008.

Electron transfer in biological systems.

Marques H J Biol Inorg Chem. 2024; 29(7-8):641-683.

PMID: 39424709 PMC: 11638306. DOI: 10.1007/s00775-024-02076-8.

The epigenetic signatures of opioid addiction and physical dependence are prevented by D-cysteine ethyl ester and betaine.

McDonough J, Singhal N, Getsy P, Knies K, Knauss Z, Mueller D Front Pharmacol. 2024; 15:1416701.

PMID: 39281282 PMC: 11392886. DOI: 10.3389/fphar.2024.1416701.

References

Kragten E, Lalande I, Zimmermann K, Roggo S, Schindler P, Muller D . Glyceraldehyde-3-phosphate dehydrogenase, the putative target of the antiapoptotic compounds CGP 3466 and R-(-)-deprenyl. J Biol Chem. 1998; 273(10):5821-8. DOI: 10.1074/jbc.273.10.5821. View

Maarsingh H, Zuidhof A, Bos I, van Duin M, Boucher J, Zaagsma J . Arginase inhibition protects against allergen-induced airway obstruction, hyperresponsiveness, and inflammation. Am J Respir Crit Care Med. 2008; 178(6):565-73. DOI: 10.1164/rccm.200710-1588OC. View

Savidge T, Newman P, Pothoulakis C, Ruhl A, Neunlist M, Bourreille A . Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione. Gastroenterology. 2007; 132(4):1344-58. DOI: 10.1053/j.gastro.2007.01.051. View

Reynaert N, Ckless K, Korn S, Vos N, Guala A, Wouters E . Nitric oxide represses inhibitory kappaB kinase through S-nitrosylation. Proc Natl Acad Sci U S A. 2004; 101(24):8945-50. PMC: 428452. DOI: 10.1073/pnas.0400588101. View

Sugita H, Fujimoto M, Yasukawa T, Shimizu N, Sugita M, Yasuhara S . Inducible nitric-oxide synthase and NO donor induce insulin receptor substrate-1 degradation in skeletal muscle cells. J Biol Chem. 2005; 280(14):14203-11. DOI: 10.1074/jbc.M411226200. View

Bhandari V, Choo-Wing R, Chapoval S, Lee C, Tang C, Kim Y . Essential role of nitric oxide in VEGF-induced, asthma-like angiogenic, inflammatory, mucus, and physiologic responses in the lung. Proc Natl Acad Sci U S A. 2006; 103(29):11021-6. PMC: 1544167. DOI: 10.1073/pnas.0601057103. View

Taylor R, Zimmerman J, Dellinger R, Straube R, Criner G, Davis Jr K . Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. JAMA. 2004; 291(13):1603-9. DOI: 10.1001/jama.291.13.1603. View

Minetti G, Colussi C, Adami R, Serra C, Mozzetta C, Parente V . Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors. Nat Med. 2006; 12(10):1147-50. DOI: 10.1038/nm1479. View

Sun J, Xin C, Eu J, Stamler J, Meissner G . Cysteine-3635 is responsible for skeletal muscle ryanodine receptor modulation by NO. Proc Natl Acad Sci U S A. 2001; 98(20):11158-62. PMC: 58700. DOI: 10.1073/pnas.201289098. View

10.

Moya M, Gow A, Califf R, Goldberg R, Stamler J . Inhaled ethyl nitrite gas for persistent pulmonary hypertension of the newborn. Lancet. 2002; 360(9327):141-3. DOI: 10.1016/S0140-6736(02)09385-6. View

11.

Stamler J, Sun Q, Hess D . A SNO storm in skeletal muscle. Cell. 2008; 133(1):33-5. DOI: 10.1016/j.cell.2008.03.013. View

12.

Bennett-Guerrero E, Veldman T, Doctor A, Telen M, Ortel T, Reid T . Evolution of adverse changes in stored RBCs. Proc Natl Acad Sci U S A. 2007; 104(43):17063-8. PMC: 2040393. DOI: 10.1073/pnas.0708160104. View

13.

Santhanam L, Christianson D, Nyhan D, Berkowitz D . Arginase and vascular aging. J Appl Physiol (1985). 2008; 105(5):1632-42. PMC: 2584835. DOI: 10.1152/japplphysiol.90627.2008. View

14.

Kwon H, Kim M, Edenberg H, Hur M . Sp3 and Sp4 can repress transcription by competing with Sp1 for the core cis-elements on the human ADH5/FDH minimal promoter. J Biol Chem. 1998; 274(1):20-8. DOI: 10.1074/jbc.274.1.20. View

15.

Whalen E, Foster M, Matsumoto A, Ozawa K, Violin J, Que L . Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2. Cell. 2007; 129(3):511-22. DOI: 10.1016/j.cell.2007.02.046. View

16.

McMahon T, Moon R, Luschinger B, Carraway M, Stone A, Stolp B . Nitric oxide in the human respiratory cycle. Nat Med. 2002; 8(7):711-7. DOI: 10.1038/nm718. View

17.

Ye Y, Martinez J, Perez-Polo R, Lin Y, Uretsky B, Birnbaum Y . The role of eNOS, iNOS, and NF-kappaB in upregulation and activation of cyclooxygenase-2 and infarct size reduction by atorvastatin. Am J Physiol Heart Circ Physiol. 2008; 295(1):H343-51. DOI: 10.1152/ajpheart.01350.2007. View

18.

Xuan Y, Guo Y, Zhu Y, Han H, Langenbach R, Dawn B . Mechanism of cyclooxygenase-2 upregulation in late preconditioning. J Mol Cell Cardiol. 2003; 35(5):525-37. PMC: 3210730. DOI: 10.1016/s0022-2828(03)00076-2. View

19.

Pauli J, Ropelle E, Cintra D, Carvalho-Filho M, Moraes J, De Souza C . Acute physical exercise reverses S-nitrosation of the insulin receptor, insulin receptor substrate 1 and protein kinase B/Akt in diet-induced obese Wistar rats. J Physiol. 2007; 586(2):659-71. PMC: 2375587. DOI: 10.1113/jphysiol.2007.142414. View

20.

Atar S, Ye Y, Lin Y, Freeberg S, Nishi S, Rosanio S . Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2. Am J Physiol Heart Circ Physiol. 2005; 290(5):H1960-8. DOI: 10.1152/ajpheart.01137.2005. View