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Proteomic method identifies proteins nitrated in vivo during inflammatory challenge
Open accessAbstract
Inflammation in asthma, sepsis, transplant rejection, and many neurodegenerative diseases associates an up-regulation of NO synthesis with increased protein nitration at tyrosine. Nitration can cause protein dysfunction and is implicated in pathogenesis, but few proteins that appear nitrated in vivo have been identified. To understand how this modification impacts physiology and disease, we used a proteomic approach toward targets of protein nitration in both in vivo and cell culture inflammatory disease models. This approach identified more than 40 nitrotyrosine-immunopositive proteins, including 30 not previously identified, that became modified as a consequence of the inflammatory response. These targets include proteins involved in oxidative stress, apoptosis, ATP production, and other metabolic functions. Our approach provides a means toward obtaining a comprehensive view of the nitroproteome and promises to broaden understanding of how NO regulates cellular processes.
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“Although a growing number of proteins have now been shown to be nitrated, multiple studies have shown that nitration is a selective process (47, 484).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [47]
In the citing paper
“Interestingly, the nitroproteome appears to be quite specific, and pathological responses may be due to modification of particularly sensitive proteins, including those that regulate signaling and cell metabolism (49–52).”
From What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology (2010) · cites this paper as [52]
In the citing paper
“Interestingly, the nitroproteome appears to be quite specific, and pathological responses may be due to modification of particularly sensitive proteins, including those that regulate signaling and cell metabolism (49–52).”
From What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology (2010) · cites this paper as [52]
In the citing paper
“Peroxynitrite and reactive species derived from it (e.g., nitrogen dioxide) are important in inflammatory responses [85] and can modulate cell signaling [87-90], in part by promoting the oxidation or nitration of a broad range of biomolecules [62].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [90]
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Metadata
- Authors
- Aulak, K. S., Miyagi, M., Yan, L., West, K. A., Massillon, D., Crabb, J. W., & Stuehr, D. J.
- Affiliations
- Cleveland Clinic (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-10-02
- Volume
- 98
- Issue
- 21
- Pages
- 12056-12061
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC59826
- OpenAlex
- W1980805550
- Cited by
- 350
- References
- 51
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 1 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 9 · 2016: 13 · 2015: 8 · 2014: 14 · 2013: 12 · 2012: 14
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Cleveland Clinic
- Cleveland Clinic Foundation
- National Institutes of Health (5r21ns041644-02, CA53914, EY06603)
- National Eye Institute (EY06603, F32EY006603, R01EY006603)
- National Cancer Institute (CA-53914, R01CA053914)
- National Institute of General Medical Sciences (GM51491, R01GM051491)
- National Institute of Neurological Disorders and Stroke (NS41644)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- protein nitration, nitrotyrosine, nitric oxide, inflammation, oxidative stress, apoptosis, ATP production, metabolic proteins, asthma, sepsis, graft rejection, neurodegenerative diseases
- MeSH terms
- Animals, Humans, Interferon-gamma, Interleukin-1, Nitrates, Nitric Oxide, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Electrophoresis, Gel, Two-Dimensional, Gene Expression, Rats, Sprague-Dawley, Nitric Oxide Synthase, Proteome, Rats, Nitric Oxide Synthase Type II
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