Acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus-dependent cognitive impairment

IntroductionChronic intermittent hypoxia (CIH) can negatively affect hippocampal function through various molecular mechanisms. Protein acetylation, a frequently occurring modification, plays crucial roles in synaptic plasticity and cognitive processes. However, the global protein acetylation induce...

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Main Authors: Fan Liu, Weiheng Yan, Chen Chen, Yubing Zeng, Yaru Kong, Xuejia He, Pei Pei, Shan Wang, Ting Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-02-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2024.1324458/full
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author Fan Liu
Fan Liu
Fan Liu
Weiheng Yan
Chen Chen
Yubing Zeng
Yubing Zeng
Yaru Kong
Xuejia He
Pei Pei
Shan Wang
Shan Wang
Shan Wang
Shan Wang
Ting Zhang
Ting Zhang
Ting Zhang
Ting Zhang
author_facet Fan Liu
Fan Liu
Fan Liu
Weiheng Yan
Chen Chen
Yubing Zeng
Yubing Zeng
Yaru Kong
Xuejia He
Pei Pei
Shan Wang
Shan Wang
Shan Wang
Shan Wang
Ting Zhang
Ting Zhang
Ting Zhang
Ting Zhang
author_sort Fan Liu
collection DOAJ
description IntroductionChronic intermittent hypoxia (CIH) can negatively affect hippocampal function through various molecular mechanisms. Protein acetylation, a frequently occurring modification, plays crucial roles in synaptic plasticity and cognitive processes. However, the global protein acetylation induced by CIH in the hippocampus and its specific effects on hippocampal function and behavior remain poorly understood.MethodsTo address this gap, we conducted a study using liquid chromatography-tandem mass spectrometry to analyze the lysine acetylome and proteome of the hippocampus in healthy adult mice exposed to intermittent hypoxia for 4 weeks (as a CIH model) compared to normoxic mice (as a control).ResultsWe identified and quantified a total of 2,184 lysine acetylation sites in 1,007 proteins. Analysis of these acetylated proteins revealed disturbances primarily in oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and glycolysis, all of which are localized exclusively to mitochondria. Additionally, we observed significant changes in the abundance of 21 proteins, some of which are known to be associated with cognitive impairments.DiscussionThis study helps to elucidate the molecular mechanisms underlying CIH-induced changes in protein acetylation in the hippocampus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hippocampal function, our findings contribute to a better understanding of the consequences of CIH-induced changes in protein acetylation in the hippocampus and the potential role of CIH in cognitive impairment.
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spelling doaj.art-ae8804e04f364a63979d661268cbc22f2024-02-22T05:19:16ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992024-02-011710.3389/fnmol.2024.13244581324458Acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus-dependent cognitive impairmentFan Liu0Fan Liu1Fan Liu2Weiheng Yan3Chen Chen4Yubing Zeng5Yubing Zeng6Yaru Kong7Xuejia He8Pei Pei9Shan Wang10Shan Wang11Shan Wang12Shan Wang13Ting Zhang14Ting Zhang15Ting Zhang16Ting Zhang17Children’s Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, ChinaGraduate School of Peking Union Medical College, Beijing, ChinaChildren’s Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, ChinaChildren’s Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, ChinaChildren’s Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, ChinaChildren’s Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, ChinaGraduate School of Peking Union Medical College, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, ChinaChildren’s Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, ChinaGraduate School of Peking Union Medical College, Beijing, ChinaBeijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, ChinaIntroductionChronic intermittent hypoxia (CIH) can negatively affect hippocampal function through various molecular mechanisms. Protein acetylation, a frequently occurring modification, plays crucial roles in synaptic plasticity and cognitive processes. However, the global protein acetylation induced by CIH in the hippocampus and its specific effects on hippocampal function and behavior remain poorly understood.MethodsTo address this gap, we conducted a study using liquid chromatography-tandem mass spectrometry to analyze the lysine acetylome and proteome of the hippocampus in healthy adult mice exposed to intermittent hypoxia for 4 weeks (as a CIH model) compared to normoxic mice (as a control).ResultsWe identified and quantified a total of 2,184 lysine acetylation sites in 1,007 proteins. Analysis of these acetylated proteins revealed disturbances primarily in oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and glycolysis, all of which are localized exclusively to mitochondria. Additionally, we observed significant changes in the abundance of 21 proteins, some of which are known to be associated with cognitive impairments.DiscussionThis study helps to elucidate the molecular mechanisms underlying CIH-induced changes in protein acetylation in the hippocampus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hippocampal function, our findings contribute to a better understanding of the consequences of CIH-induced changes in protein acetylation in the hippocampus and the potential role of CIH in cognitive impairment.https://www.frontiersin.org/articles/10.3389/fnmol.2024.1324458/fullcognitionlysine acetylationCIHhippocampusmitochondria
spellingShingle Fan Liu
Fan Liu
Fan Liu
Weiheng Yan
Chen Chen
Yubing Zeng
Yubing Zeng
Yaru Kong
Xuejia He
Pei Pei
Shan Wang
Shan Wang
Shan Wang
Shan Wang
Ting Zhang
Ting Zhang
Ting Zhang
Ting Zhang
Acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus-dependent cognitive impairment
Frontiers in Molecular Neuroscience
cognition
lysine acetylation
CIH
hippocampus
mitochondria
title Acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus-dependent cognitive impairment
title_full Acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus-dependent cognitive impairment
title_fullStr Acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus-dependent cognitive impairment
title_full_unstemmed Acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus-dependent cognitive impairment
title_short Acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus-dependent cognitive impairment
title_sort acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus dependent cognitive impairment
topic cognition
lysine acetylation
CIH
hippocampus
mitochondria
url https://www.frontiersin.org/articles/10.3389/fnmol.2024.1324458/full
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