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Cited by 36Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisRedox biology and oxidative stressNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Oxidative Modifications of Protein Tyrosyl Residues Are Increased in Plasma of Human Subjects with Interstitial Lung Disease

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Pennathur, Subramaniam, Vivekanandan-Giri, Anuradha, Locy, Morgan L., Kulkarni, Tejaswini, Zhi, Degui, Zeng, Lixia, Byun, Jaeman, de Andrade, Joao A. +1 more·2016·American Journal of Respiratory and Critical Care Medicine
DOI 10.1164/rccm.201505-0992ocPMC PMC4849179
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Abstract

Rationale: Interstitial lung diseases (ILDs) are associated with oxidative stress. Plasma biomarkers that are directly linked to oxidative stress responses in this disease have not been identified. Stable oxidation products of tyrosine residues in proteins may reflect the oxidative microenvironment in the lung or a systemic inflammatory state. Objectives: To determine if levels of protein tyrosine oxidation are elevated in plasma of patients with ILD compared with an age- and sex-matched healthy control cohort. Methods: Three tyrosine oxidation products (3-chlorotyrosine, 3-nitrotyrosine, and o,o′-dityrosine) were quantified by tandem mass spectrometry in cellular models, a mouse model of injury-induced fibrosis, and in plasma of healthy control subjects and patients with ILD (n = 42 in each group). Measurements and Main Results: Plasma levels of 3-chlorotyrosine, 3-nitrotyrosine, and o,o′-dityrosine were markedly elevated in patients with ILD compared with control subjects with receiver operating characteristic curves separating these groups of 0.872, 0.893, and 0.997, respectively. In a murine model of lung fibrosis, levels of all three oxidative tyrosine modifications were increased in plasma and lung tissue. Cellular models support a critical role for a heme peroxidase and enzymatic sources of reactive oxygen species in the generation of these oxidized products. Conclusions: We demonstrate an increase in oxidized tyrosine moieties within proteins in the circulating plasma of patients with ILD. These data support the potential for development of oxidative stress–related biomarkers in early diagnosis, prognostication, and/or in evaluating responsiveness to emerging therapies for ILD.

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Authors
Pennathur, S., Vivekanandan-Giri, A., Locy, M. L., Kulkarni, T., Zhi, D., Zeng, L., Byun, J., de Andrade, J. A., & Thannickal, V. J.
Affiliations
  • University of Michigan (US)
  • Division of Nephrology
  • Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and
  • University of Alabama at Birmingham (US)
Corresponding author
Thannickal, Victor J.
ORCID
Venue
American Journal of Respiratory and Critical Care Medicine
Publisher
Oxford University Press (OUP)
Published
2016-04
Volume
193
Issue
8
Pages
861-868
ISSN
  • 1073-449X (ISSN-L)
  • 1535-4970
DOI
10.1164/rccm.201505-0992oc
PMC
PMC4849179
OpenAlex
W2173886356
Cited by
36
References
3
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 2 · 2018: 7 · 2017: 6 · 2016: 4
FWCI
4.49
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • American Journal of Respiratory and Critical Care Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (R01 HL094230, P30 DK89503, U24 DK097153, R01 AG046210, P01 HL114470)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
interstitial lung disease, oxidative stress, 3-chlorotyrosine, nitrotyrosine, plasma biomarkers, pulmonary fibrosis, heme peroxidase, reactive oxygen species
MeSH terms
Animals, Cells, Cultured, Female, Humans, Male, Mice, Inbred C57BL, Middle Aged, Tyrosine, Biomarkers, Lung Diseases, Interstitial, Oxidative Stress, Mice, Tandem Mass Spectrometry

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