Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains

Yilin Tang,1,* Sha Han,1,* Tetsuya Asakawa,2,3 Yunhe Luo,1 Xiang Han,1 Baoguo Xiao,4 Qiang Dong,1,4 Liang Wang1,41Department of Neurology, Huashan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Neurosurgery, 3Department of Psychiatry, Hamamatsu Universit...

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Autores principales:	Tang YL, Han S, Asakawa T, Luo YH, Han X, Xiao BG, Dong Q, Wang L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Intracerebral hemorrhage DNA hydroxymethylation Tet protein Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/4ef21bfa88b948ab81da571e81e8c23c
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spelling	oai:doaj.org-article:4ef21bfa88b948ab81da571e81e8c23c2021-12-02T08:21:31ZEffects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains1178-2021https://doaj.org/article/4ef21bfa88b948ab81da571e81e8c23c2016-03-01T00:00:00Zhttps://www.dovepress.com/effects-of-intracerebral-hemorrhage-on-5-hydroxymethylcytosine-modific-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Yilin Tang,1,* Sha Han,1,* Tetsuya Asakawa,2,3 Yunhe Luo,1 Xiang Han,1 Baoguo Xiao,4 Qiang Dong,1,4 Liang Wang1,41Department of Neurology, Huashan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Neurosurgery, 3Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan; 4Institute of Neurology, Huashan Hospital of Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: The past decade has resulted in an increase in the knowledge of molecular mechanisms underlying brain injury induced by intracerebral hemorrhage (ICH). Recent advances have provided a link between epigenetic modification and the regulation of gene expression. 5-hydroxymethylcytosine (5hmC) converted from 5-methylcytosine by the ten-eleven translocation (TET) family of proteins has emerged as a new epigenetic modification. While the dynamics of 5hmC during cerebral ischemia have recently been reported, whether 5hmC is involved in ICH remains unexplored. In this study, we investigated the effects of ICH on DNA hydroxymethylation. We showed that the global level of 5hmC rapidly decreased as early as 24 hours after ICH and persisted until 72 hours. Furthermore, the level of 5hmC in the CpG-rich regions of Akt2, Pdpk1 and Vegf genes was significantly decreased with a minimum level observed at 48 hours or 72 hours. Decreased 5hmC was observed in parallel with an increase in 5-methylcytosine over this time course, and mRNA levels of Akt2, Pdpk1 and Vegf were downregulated upon ICH injury. Finally, Tet1, Tet2 and Tet3 mRNA levels were dramatically decreased in the ICH brain. Our study for the first time established the correlation between DNA hydroxymethylation and ICH injury. Further investigations should examine whether 5hmC modification could be a therapeutic target for the treatment of ICH injury.Keywords: stroke, cerebral edema, DNA hydroxymethylation, TET proteinTang YLHan SAsakawa TLuo YHHan XXiao BGDong QWang LDove Medical PressarticleIntracerebral hemorrhageDNA hydroxymethylationTet proteinNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2016, Iss Issue 1, Pp 617-624 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Intracerebral hemorrhage DNA hydroxymethylation Tet protein Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Intracerebral hemorrhage DNA hydroxymethylation Tet protein Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Tang YL Han S Asakawa T Luo YH Han X Xiao BG Dong Q Wang L Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains
description	Yilin Tang,1,* Sha Han,1,* Tetsuya Asakawa,2,3 Yunhe Luo,1 Xiang Han,1 Baoguo Xiao,4 Qiang Dong,1,4 Liang Wang1,41Department of Neurology, Huashan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Neurosurgery, 3Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan; 4Institute of Neurology, Huashan Hospital of Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: The past decade has resulted in an increase in the knowledge of molecular mechanisms underlying brain injury induced by intracerebral hemorrhage (ICH). Recent advances have provided a link between epigenetic modification and the regulation of gene expression. 5-hydroxymethylcytosine (5hmC) converted from 5-methylcytosine by the ten-eleven translocation (TET) family of proteins has emerged as a new epigenetic modification. While the dynamics of 5hmC during cerebral ischemia have recently been reported, whether 5hmC is involved in ICH remains unexplored. In this study, we investigated the effects of ICH on DNA hydroxymethylation. We showed that the global level of 5hmC rapidly decreased as early as 24 hours after ICH and persisted until 72 hours. Furthermore, the level of 5hmC in the CpG-rich regions of Akt2, Pdpk1 and Vegf genes was significantly decreased with a minimum level observed at 48 hours or 72 hours. Decreased 5hmC was observed in parallel with an increase in 5-methylcytosine over this time course, and mRNA levels of Akt2, Pdpk1 and Vegf were downregulated upon ICH injury. Finally, Tet1, Tet2 and Tet3 mRNA levels were dramatically decreased in the ICH brain. Our study for the first time established the correlation between DNA hydroxymethylation and ICH injury. Further investigations should examine whether 5hmC modification could be a therapeutic target for the treatment of ICH injury.Keywords: stroke, cerebral edema, DNA hydroxymethylation, TET protein
format	article
author	Tang YL Han S Asakawa T Luo YH Han X Xiao BG Dong Q Wang L
author_facet	Tang YL Han S Asakawa T Luo YH Han X Xiao BG Dong Q Wang L
author_sort	Tang YL
title	Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains
title_short	Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains
title_full	Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains
title_fullStr	Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains
title_full_unstemmed	Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains
title_sort	effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/4ef21bfa88b948ab81da571e81e8c23c
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Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains

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