Effect of aging on 5-hydroxymethylcytosine in brain mitochondria

被引：173

作者：

Dzitoyeva, Svetlana ^{[1
]}

Chen, Hu ^{[1
]}

Manev, Hari ^{[1
]}

机构：

[1] Univ Illinois, Dept Psychiat, Inst Psychiat, 1601 W Taylor St,M-C912, Chicago, IL 60612 USA

来源：

NEUROBIOLOGY OF AGING | 2012年 / 33卷 / 12期

基金：

美国国家卫生研究院;

关键词：

Mitochondrial epigenetics; Mitochondrial DNA (mtDNA); Ten-eleven-translocation (TET); DNA methyltransferase 1 (DNMT1); 5-Hydroxymethylcytosine (5hmC); 5-Methylcytosine (5mC); Brain; Frontal cortex; Cerebellum; Aging; INCREASED OXIDATIVE DAMAGE; DNA METHYLATION; EPIGENETIC MECHANISMS; NUCLEAR; 5-METHYLCYTOSINE; BASE; TRANSCRIPTION; NEURONS; ENZYMES; AGE;

D O I：

10.1016/j.neurobiolaging.2012.02.006

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Nuclear epigenetics of the mammalian brain is modified during aging. Little is known about epigenetic modifications of mitochondrial DNA (mtDNA). We analyzed brain samples of 4- and 24-month-old mice and found that aging decreased mtDNA 5-hydroxymethylcytosine (5hmC) but not 5-methylcytosine (5mC) levels in the frontal cortex but not the cerebellum. Transcript levels of selected mtDNA-encoded genes increased during aging in the frontal cortex only. Aging affected the expression of enzymes involved in 5-methylcytosine and 5-hydroxymethylcytosine synthesis (mitochondrial DNA methyltransferase 1 [mtDNMT1] and ten-eleven-translocation [TET]1-TET3, respectively). In the frontal cortex, aging decreased mtDNMT1 messenger RNA (mRNA) levels without affecting TET1-TET3 mRNAs. In the cerebellum, TET2 and TET3 mRNA content was increased but mtDNMT1 mRNA was unaffected. Using Western immunoblotting of samples from primary neuronal cultures, we found TET immunoreactivity in the mitochondrial fraction. At the single cell level, TET immunoreactivity was detected in the nucleus and in the perinuclear/intraneurite areas where it frequently colocalized with a mitochondrial marker. Our results demonstrated the presence and susceptibility to aging of mitochondrial epigenetic mechanisms in the mammalian brain. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：2881 / 2891

页数：11

共 44 条

[1] PERVASIVE CPG SUPPRESSION IN ANIMAL MITOCHONDRIAL GENOMES [J].

CARDON, LR ;

BURGE, C ;

CLAYTON, DA ;

KARLIN, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (09) :3799-3803

[2] 5-methylcytosine attack by hydroxyl free radicals and during carbon tetrachloride promoted liver microsomal lipid peroxidation: Structure of reaction products [J].

Castro, GD ;

Gomez, MID ;

Castro, JA .

CHEMICO-BIOLOGICAL INTERACTIONS, 1996, 99 (1-3) :289-299

[3] 5-LIPDXYGENASE IN MOUSE CEREBELLAR Purkinje CELLS [J].

Chen, H. ;

Dzitoyeva, S. ;

Manev, H. .

NEUROSCIENCE, 2010, 171 (02) :383-389

[4] Mitochondria and neuroplasticity [J].

Cheng, Aiwu ;

Hou, Yan ;

Mattson, Mark P. .

ASN NEURO, 2010, 2 (05) :243-256

[5] Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction [J].

Chouliaras, Leonidas ;

van den Hove, Daniel L. A. ;

Kenis, Gunter ;

Keitel, Stella ;

Hof, Patrick R. ;

van Os, Jim ;

Steinbusch, Harry W. M. ;

Schmitz, Christoph ;

Rutten, Bart P. F. .

NEUROBIOLOGY OF AGING, 2012, 33 (08) :1672-1681

[6] Advances in DNA methylation: 5-hydroxymethylcytosine revisited [J].

Dahl, Christina ;

Gronbaek, Kirsten ;

Guldberg, Per .

CLINICA CHIMICA ACTA, 2011, 412 (11-12) :831-836

[7] High Sensitivity 5-hydroxymethylcytosine Detection in Balb/C Brain Tissue [J].

Davis, Theodore ;

Vaisvila, Romualdas .

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2011, (48)

[8] Cognitive neuroepigenetics: A role for epigenetic mechanisms in learning and memory [J].

Day, Jeremy J. ;

Sweatt, J. David .

NEUROBIOLOGY OF LEARNING AND MEMORY, 2011, 96 (01) :2-12

[9] 5-Lipoxygenase DNA Methylation and mRNA Content in the Brain and Heart of Young and Old Mice [J].

Dzitoyeva, Svetlana ;

Imbesi, Marta ;

Ng, Louisa W. ;

Manev, Hari .

NEURAL PLASTICITY, 2009, 2009 :209596

[10] DNA replication and transcription in mammalian mitochondria [J].

Falkenberg, Maria ;

Larsson, Nils-Goeran ;

Gustafsson, Claes M. .

ANNUAL REVIEW OF BIOCHEMISTRY, 2007, 76 :679-699

← 1 2 3 4 5 →