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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Main Authors: Yuan-Hong Deng, Xin-Xiao Zhang, Chuan-Yuan Tao, Yan-Jing Liang, Jing Yuan, Su-Hao Yang, Yuan-Rui Yang, Xiao-Yi Xiong
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0259798
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author Yuan-Hong Deng
Xin-Xiao Zhang
Chuan-Yuan Tao
Yan-Jing Liang
Jing Yuan
Su-Hao Yang
Yuan-Rui Yang
Xiao-Yi Xiong
author_facet Yuan-Hong Deng
Xin-Xiao Zhang
Chuan-Yuan Tao
Yan-Jing Liang
Jing Yuan
Su-Hao Yang
Yuan-Rui Yang
Xiao-Yi Xiong
author_sort Yuan-Hong Deng
collection DOAJ
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 doaj.art-a8ea332d5d1a43199a4d9a5df411c9192022-12-21T18:14:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-011611e025979810.1371/journal.pone.0259798Succinylation profiles of brain injury after intracerebral hemorrhage.Yuan-Hong DengXin-Xiao ZhangChuan-Yuan TaoYan-Jing LiangJing YuanSu-Hao YangYuan-Rui YangXiao-Yi XiongProtein 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.https://doi.org/10.1371/journal.pone.0259798
spellingShingle Yuan-Hong Deng
Xin-Xiao Zhang
Chuan-Yuan Tao
Yan-Jing Liang
Jing Yuan
Su-Hao Yang
Yuan-Rui Yang
Xiao-Yi Xiong
Succinylation profiles of brain injury after intracerebral hemorrhage.
PLoS ONE
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
url https://doi.org/10.1371/journal.pone.0259798
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