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Succinylation profiles of brain injury after intracerebral hemorrhage

Protein posttranslational modifications (PTMs) regulate the biological processes of human diseases by genetic code expansion and cellular pathophysiology regulation; however, system-wide changes in PTM levels in the intracerebral hemorrhage (ICH) brain remain poorly understood. Succinylation refers...

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Autores principales: Deng, Yuan-Hong, Zhang, Xin-Xiao, Tao, Chuan-Yuan, Liang, Yan-Jing, Yuan, Jing, Yang, Su-Hao, Yang, Yuan-Rui, Xiong, Xiao-Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592435/
https://www.ncbi.nlm.nih.gov/pubmed/34780519
http://dx.doi.org/10.1371/journal.pone.0259798
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author Deng, Yuan-Hong
Zhang, Xin-Xiao
Tao, Chuan-Yuan
Liang, Yan-Jing
Yuan, Jing
Yang, Su-Hao
Yang, Yuan-Rui
Xiong, Xiao-Yi
author_facet Deng, Yuan-Hong
Zhang, Xin-Xiao
Tao, Chuan-Yuan
Liang, Yan-Jing
Yuan, Jing
Yang, Su-Hao
Yang, Yuan-Rui
Xiong, Xiao-Yi
author_sort Deng, Yuan-Hong
collection PubMed
description Protein posttranslational modifications (PTMs) regulate the biological processes of human diseases by genetic code expansion and cellular pathophysiology regulation; however, system-wide changes in PTM levels in the intracerebral hemorrhage (ICH) brain remain poorly understood. Succinylation refers to a major PTM during the regulation of multiple biological processes. In this study, according to the methods of quantitative succinyllysine proteomics based on high-resolution mass spectrometry, we investigated ICH-associated brain protein succinyllysine modifications and obtained 3,680 succinylated sites and quantified around 3,530 sites. Among them, 25 succinyllysine sites on 23 proteins were upregulated (hypersuccinylated), whereas 13 succinyllysine sites on 12 proteins were downregulated (hyposuccinylated) following ICH. The cell component enrichment analysis of these succinylproteins with significant changes showed that 58.3% of the hyposuccinylated proteins were observed in the mitochondria, while the hyper-succinylproteins located in mitochondria decreased in the percentage to about 35% in ICH brains with a concomitant increase in the percentage of cytoplasm to 30.4%. Further bioinformatic analysis showed that the succinylproteins were mostly mitochondria and synapse-related subcellular located and involved in many pathophysiological processes, like metabolism, synapse working, and ferroptosis. Moreover, the integrative analysis of our succinylproteomics data and previously published transcriptome data showed that the mRNAs matched by most differentially succinylated proteins were especially highly expressed in neurons, endothelial cells, and astrocytes. Our study uncovers some succinylation-affected processes and pathways in response to ICH brains and gives us novel insights into understanding pathophysiological processes of brain injury caused by ICH.
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spelling pubmed-85924352021-11-16 Succinylation profiles of brain injury after intracerebral hemorrhage Deng, Yuan-Hong Zhang, Xin-Xiao Tao, Chuan-Yuan Liang, Yan-Jing Yuan, Jing Yang, Su-Hao Yang, Yuan-Rui Xiong, Xiao-Yi PLoS One Research Article Protein posttranslational modifications (PTMs) regulate the biological processes of human diseases by genetic code expansion and cellular pathophysiology regulation; however, system-wide changes in PTM levels in the intracerebral hemorrhage (ICH) brain remain poorly understood. Succinylation refers to a major PTM during the regulation of multiple biological processes. In this study, according to the methods of quantitative succinyllysine proteomics based on high-resolution mass spectrometry, we investigated ICH-associated brain protein succinyllysine modifications and obtained 3,680 succinylated sites and quantified around 3,530 sites. Among them, 25 succinyllysine sites on 23 proteins were upregulated (hypersuccinylated), whereas 13 succinyllysine sites on 12 proteins were downregulated (hyposuccinylated) following ICH. The cell component enrichment analysis of these succinylproteins with significant changes showed that 58.3% of the hyposuccinylated proteins were observed in the mitochondria, while the hyper-succinylproteins located in mitochondria decreased in the percentage to about 35% in ICH brains with a concomitant increase in the percentage of cytoplasm to 30.4%. Further bioinformatic analysis showed that the succinylproteins were mostly mitochondria and synapse-related subcellular located and involved in many pathophysiological processes, like metabolism, synapse working, and ferroptosis. Moreover, the integrative analysis of our succinylproteomics data and previously published transcriptome data showed that the mRNAs matched by most differentially succinylated proteins were especially highly expressed in neurons, endothelial cells, and astrocytes. Our study uncovers some succinylation-affected processes and pathways in response to ICH brains and gives us novel insights into understanding pathophysiological processes of brain injury caused by ICH. Public Library of Science 2021-11-15 /pmc/articles/PMC8592435/ /pubmed/34780519 http://dx.doi.org/10.1371/journal.pone.0259798 Text en © 2021 Deng et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Deng, Yuan-Hong
Zhang, Xin-Xiao
Tao, Chuan-Yuan
Liang, Yan-Jing
Yuan, Jing
Yang, Su-Hao
Yang, Yuan-Rui
Xiong, Xiao-Yi
Succinylation profiles of brain injury after intracerebral hemorrhage
title Succinylation profiles of brain injury after intracerebral hemorrhage
title_full Succinylation profiles of brain injury after intracerebral hemorrhage
title_fullStr Succinylation profiles of brain injury after intracerebral hemorrhage
title_full_unstemmed Succinylation profiles of brain injury after intracerebral hemorrhage
title_short Succinylation profiles of brain injury after intracerebral hemorrhage
title_sort succinylation profiles of brain injury after intracerebral hemorrhage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592435/
https://www.ncbi.nlm.nih.gov/pubmed/34780519
http://dx.doi.org/10.1371/journal.pone.0259798
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