Effect of aging on 5-hydroxymethylcytosine in brain mitochondria.
Effect of aging on 5-hydroxymethylcytosine in brain mitochondria.
复制标题
衰老对脑线粒体中5-羟基环霉素的影响。
DOI：
10.1016/j.neurobiolaging.2012.02.006
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发表时间：
2012-12
影响因子：
4.2
通讯作者：
Manev H
中科院分区：
文献类型：
--
作者：
Dzitoyeva S;Chen H;Manev H
哺乳动物大脑的核表观遗传学在衰老过程中发生改变。关于线粒体DNA （mtDNA）的表观遗传修饰知之甚少。我们分析了4个月和24个月大的小鼠的大脑样本，发现衰老降低了额叶皮层的mtDNA 5-羟甲基胞嘧啶（5hmC）水平，而不是5-甲基胞嘧啶（5mC）水平，而不是小脑。选择性mtdna编码基因的转录水平在衰老过程中仅在额叶皮层增加。衰老影响了5-甲基胞嘧啶和5-羟甲基胞嘧啶合成相关酶（线粒体DNA甲基转移酶1 [mtDNMT1]和10 - 11易位[TET]1- tet3）的表达。在额叶皮层，衰老降低mtDNMT1信使RNA （mRNA）水平，但不影响TET1-TET3 mRNA。在小脑中，TET2和TET3 mRNA含量升高，而mtDNMT1 mRNA含量未受影响。使用Western免疫印迹法对原代神经元培养样本进行检测，我们发现线粒体部分具有TET免疫反应性。在单细胞水平，TET免疫反应性在细胞核和核周/神经内膜区域被检测到，它经常与线粒体标记物共定位。我们的研究结果证明了哺乳动物大脑中线粒体表观遗传机制的存在及其对衰老的易感性。
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.
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影响因子：
4.7
作者：
Manczak, M;Jung, YS;Reddy, PH
通讯作者：
Reddy, PH
DOI：
10.1073/pnas.1012311108
发表时间：
2011-03-01
影响因子：
11.1
作者：
Shock, Lisa S.;Thakkar, Prashant V.;Taylor, Shirley M.
通讯作者：
Taylor, Shirley M.
影响因子：
4.2
作者：
Chouliaras L;van den Hove DL;Kenis G;Keitel S;Hof PR;van Os J;Steinbusch HW;Schmitz C;Rutten BP
通讯作者：
Rutten BP
影响因子：
2.7
作者：
Day, Jeremy J;Sweatt, J David
通讯作者：
Sweatt, J David
影响因子：
14.9
作者：
Jin SG;Kadam S;Pfeifer GP
通讯作者：
Pfeifer GP