Mutations in mitochondrial DNA accumulate differentially in three different human tissues during ageing
Mutations in mitochondrial DNA accumulate differentially in three different human tissues during ageing
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DOI：
10.1093/nar/26.5.1268
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发表时间：
1998-03-01
影响因子：
14.9
通讯作者：
Nagley, P
中科院分区：
文献类型：
--
作者：
Liu, VWS;Zhang, CF;Nagley, P
在60个人体组织样本中（包括骨骼肌、心脏和肾脏），我们使用定量PCR方法对携带4977 bp缺失的线粒体DNA（mtDNA）分子进行定量。（mtDNA（4977））和3243 A->G碱基替换，此外，以半定量方式评估多个mtDNA缺失的患病率，对于所有三种组织，特定mtDNA突变的积累与受试者的年龄之间的相关性是高度显著的，然而，观察到两种特定突变在各种组织中的积累程度不同，因此，平均丰度在一个年龄匹配的成年人亚组中，mtDNA（4977）的突变率（占总mtDNA的百分比）在骨骼肌中明显高于心脏和肾脏，然而，发现骨骼肌中3243 A->G突变的平均丰度低于心脏和肾脏。从成人骨骼肌提取的DNA中的多个mtDNA缺失产生的PCR产物阵列的可视化在30个PCR循环后容易地进行。相比之下，在从成人心脏或肾脏提取的DNA中，需要扩增35个PCR循环来检测多个mtDNA缺失，尽管这样的多个缺失在心脏和肾脏中比在骨骼肌中少，在所有组织提取物中，存在独特的条带模式，甚至来自同一受试者的不同组织。mtDNA（4977）、其他mtDNA缺失和3243 A->G突变在所分析的三种组织中的差异积累大概反映了这些不同组织的不同代谢和衰老特征。
In 60 human tissue samples (encompassing skeletal muscle, heart and kidney) obtained from subjects aged from under 1 to 90 years, we used quantitative PCR procedures to quantify mitochondrial DNA (mtDNA) molecules carrying the 4977 bp deletion (mtDNA(4977)) and 3243 A-->G base substitution, In addition, the prevalence of multiple mtDNA deletions was assessed in a semi-quantitative manner, For all three tissues, the correlations between the accumulation of the particular mtDNA mutations and age of the subject are highly significant, However, differential extents of accumulation of the two specific mutations in the various tissues were observed, Thus, the mean abundance (percentage of mutant mtDNA out of total mtDNA) of mtDNA(4977) in a subset of age-matched adults is substantially higher in skeletal muscle than in heart and kidney, However, the mean abundance of the 3243 A-->G mutation in skeletal muscle was found to be lower than that in heart and kidney. Visualisation of arrays of PCR products arising from multiple mtDNA deletions in DNA extracted from adult skeletal muscle, was readily made after 30 cycles of PCR, By contrast, in DNA extracted from adult heart or kidney, amplification for 35 cycles of PCR was required to detect multiple mtDNA deletions, Although such multiple deletions are less abundant in heart and kidney than in skeletal muscle, in all tissue extracts there are unique patterns of bands, even from different tissues of the same subject. The differential accumulation of mtDNA(4977), other mtDNA deletions and the 3243 A-->G mutation in the three tissues analysed presumably reflects different metabolic and senescence characteristics of these various tissues.