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Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress
Reactive oxygen species (ROS) are increasingly recognised as important signalling molecules through oxidation of protein cysteine residues. Comprehensive identification of redox-regulated proteins and pathways is crucial to understand ROS-mediated events. Here, we present stable isotope cysteine lab...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910380/ https://www.ncbi.nlm.nih.gov/pubmed/29679077 http://dx.doi.org/10.1038/s41467-018-04003-3 |
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author | van der Reest, Jiska Lilla, Sergio Zheng, Liang Zanivan, Sara Gottlieb, Eyal |
author_facet | van der Reest, Jiska Lilla, Sergio Zheng, Liang Zanivan, Sara Gottlieb, Eyal |
author_sort | van der Reest, Jiska |
collection | PubMed |
description | Reactive oxygen species (ROS) are increasingly recognised as important signalling molecules through oxidation of protein cysteine residues. Comprehensive identification of redox-regulated proteins and pathways is crucial to understand ROS-mediated events. Here, we present stable isotope cysteine labelling with iodoacetamide (SICyLIA), a mass spectrometry-based workflow to assess proteome-scale cysteine oxidation. SICyLIA does not require enrichment steps and achieves unbiased proteome-wide sensitivity. Applying SICyLIA to diverse cellular models and primary tissues provides detailed insights into thiol oxidation proteomes. Our results demonstrate that acute and chronic oxidative stress causes oxidation of distinct metabolic proteins, indicating that cysteine oxidation plays a key role in the metabolic adaptation to redox stress. Analysis of mouse kidneys identifies oxidation of proteins circulating in biofluids, through which cellular redox stress can affect whole-body physiology. Obtaining accurate peptide oxidation profiles from complex organs using SICyLIA holds promise for future analysis of patient-derived samples to study human pathologies. |
format | Online Article Text |
id | pubmed-5910380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59103802018-04-23 Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress van der Reest, Jiska Lilla, Sergio Zheng, Liang Zanivan, Sara Gottlieb, Eyal Nat Commun Article Reactive oxygen species (ROS) are increasingly recognised as important signalling molecules through oxidation of protein cysteine residues. Comprehensive identification of redox-regulated proteins and pathways is crucial to understand ROS-mediated events. Here, we present stable isotope cysteine labelling with iodoacetamide (SICyLIA), a mass spectrometry-based workflow to assess proteome-scale cysteine oxidation. SICyLIA does not require enrichment steps and achieves unbiased proteome-wide sensitivity. Applying SICyLIA to diverse cellular models and primary tissues provides detailed insights into thiol oxidation proteomes. Our results demonstrate that acute and chronic oxidative stress causes oxidation of distinct metabolic proteins, indicating that cysteine oxidation plays a key role in the metabolic adaptation to redox stress. Analysis of mouse kidneys identifies oxidation of proteins circulating in biofluids, through which cellular redox stress can affect whole-body physiology. Obtaining accurate peptide oxidation profiles from complex organs using SICyLIA holds promise for future analysis of patient-derived samples to study human pathologies. Nature Publishing Group UK 2018-04-20 /pmc/articles/PMC5910380/ /pubmed/29679077 http://dx.doi.org/10.1038/s41467-018-04003-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article van der Reest, Jiska Lilla, Sergio Zheng, Liang Zanivan, Sara Gottlieb, Eyal Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress |
title | Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress |
title_full | Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress |
title_fullStr | Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress |
title_full_unstemmed | Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress |
title_short | Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress |
title_sort | proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910380/ https://www.ncbi.nlm.nih.gov/pubmed/29679077 http://dx.doi.org/10.1038/s41467-018-04003-3 |
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