S-Nitrosylation: Targets, Controls and Outcomes

Author(s): Bruce C. Kone

Journal Name: Current Genomics

Volume 7 , Issue 5 , 2006

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Abstract:

Nitric oxide (NO) is a potent cell signaling and effector molecule that participates in numerous physiological and pathophysiological events in a variety of cell types and tissues. NO derived from all major isoforms of NO synthase can S-nitrosylate cysteine thiols in target proteins, potentially altering their functional activities in a redox-dependent, cGMP-independent manner. Formation of protein S-nitrosocysteine adducts appears to occur through multiple pathways. Emerging evidence suggests that S-nitrosylation is a specific, reversible and regulated covalent post-translational modifi-cation that modulates diverse biological and physiological functions. In addition to altering protein activity, localization and stability, S-nitrosylation participates in the control of cellular metabolism, apoptosis, protein – protein interactions, transcription factor function, ion channel activity and cellular redox balance. Increasingly sophisticated proteomic ap-proaches used in various cell types and tissues have identified S-nitrosylation of proteins of virtually all major classes, in-cluding cytoskeletal proteins, chaperones, proteins of the translational and transcriptional machinery, vesicular transport and signaling. S-nitrosylation has also been shown to regulate the NO synthase isoforms themselves, reversibly inhibiting endothelial NO synthase activity and feedback inhibiting PARP-1, a transactivator of inducible NO synthase. Imbalances in NO metabolism and dysregulated S-nitrosylation have been implicated in a growing list of human diseases, such as neurodegenerative disorders, endotoxemic shock and insulin resistance. Here we review the key discoveries and directions in this field, including the role of S-nitrosylation as a potential therapeutic target in specific human diseases.

Keywords: NO synthase, S-Nitrosoproteome, NADPH, Diabetes Mellitus, Neurodegenerative Diseases, Pulmonary Diseases

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Article Details

VOLUME: 7
ISSUE: 5
Year: 2006
Page: [301 - 310]
Pages: 10
DOI: 10.2174/138920206778604340
Price: $65

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