Abstract
Reactive nitrogen species, such as nitric oxide (NO), exert their biological activity in large part through post-translational modification of cysteine residues, forming S-nitrosothiols. This chemical reaction proceeds via a process that we and our colleagues have termed protein S-nitrosylation. Under conditions of normal NO production, S-nitrosylation regulates the activity of many normal proteins. However, in degenerative conditions characterized by nitrosative stress, increased levels of NO lead to aberrant S-nitrosylation that contributes to the pathology of the disease. Thus, S-nitrosylation has been implicated in a wide range of cellular mechanisms, including mitochondrial function, proteostasis, transcriptional regulation, synaptic activity, and cell survival. In recent years, the research area of protein S-nitrosylation has become prominent due to improvements in the detection systems as well as the demonstration that protein S-nitrosylation plays a critical role in the pathogenesis of neurodegenerative and other neurological disorders. To further promote our understanding of how protein S-nitrosylation affects cellular systems, guidelines for the design and conduct of research on S-nitrosylated (or SNO-)proteins would be highly desirable, especially for those newly entering the field. In this review article, we provide a strategic overview of designing experimental approaches to study protein S-nitrosylation. We specifically focus on methods that can provide critical data to demonstrate that an S-nitrosylated protein plays a (patho-)physiologically-relevant role in a biological process. Hence, the implementation of the approaches described herein will contribute to further advancement of the study of S-nitrosylated proteins, not only in neuroscience but also in other research fields.
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Abbreviations
- GSNO:
-
S-Nitrosoglutathione
- MS:
-
Mass spectrometry
- NO:
-
Nitric oxide
- NOS:
-
NO synthase
- SNO:
-
S-Nitrosylation or S-nitrosothiol
- SNOC:
-
S-Nitrosocysteine
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Acknowledgments
This work was supported in part by NIH Grants P30 NS076411, R01 NS086890, R01 ES017462, P01 HD029587, and R21 NS080799 (SAL), the Brain and Behavior Research Foundation (SAL), and the Michael J. Fox Foundation (SAL and TN).
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Special Issue: In honor of Dr. Philip Beart.
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Nakamura, T., Lipton, S.A. Nitrosative Stress in the Nervous System: Guidelines for Designing Experimental Strategies to Study Protein S-Nitrosylation. Neurochem Res 41, 510–514 (2016). https://doi.org/10.1007/s11064-015-1640-z
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DOI: https://doi.org/10.1007/s11064-015-1640-z