ASSOCIATION OF MITOCHONDRIAL-DNA DAMAGE WITH AGING AND CORONARY ATHEROSCLEROTIC HEART-DISEASE
ASSOCIATION OF MITOCHONDRIAL-DNA DAMAGE WITH AGING AND CORONARY ATHEROSCLEROTIC HEART-DISEASE
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DOI：
10.1016/0921-8734(92)90021-g
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发表时间：
1992-09-01
期刊：
影响因子：
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通讯作者：
WALLACE, DC
中科院分区：
文献类型：
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作者：
CORRALDEBRINSKI, M;SHOFFNER, JM;WALLACE, DC
通过定量测定正常心脏和冠状动脉粥样硬化疾病心脏中mtDNA缺失的积累，研究了体细胞线粒体DNA （mtDNA）损伤在人类衰老和氧化磷酸化进行性疾病（OXPHOS）中的作用。在正常心脏中，mtDNA缺失出现在40岁之后，并随着年龄的增长而积累。常见的4977核苷酸对（np）缺失（mtDNA4977）最多达到0.007%，mtDNA7436和mtdna10422缺失同时出现。在冠状动脉疾病导致的线粒体底物缺失的心脏中，mtDNA4977缺失水平比年龄匹配的对照组升高了7-220倍，mtDNA7436和mtdna10422缺失平行增加。这种累积的mtDNA损伤与细胞核OXPHOS基因mRNA的代偿性3.5倍诱导有关，受最大工作量的缺血心脏区域（左心室）显示出最大的mtDNA损伤积累和OXPHOS基因诱导。这些观察结果支持了线粒体dna损伤确实随着年龄增长而累积的假设，并表明呼吸压力极大地提高了线粒体损伤。
The role of somatic mitochondrial DNA (mtDNA) damage in human aging and progressive diseases of oxidative phosphorylation (OXPHOS) was examined by quantitating the accumulation of mtDNA deletions in normal hearts and hearts with coronary atherosclerotic disease. In normal hearts, mtDNA deletions appeared after 40 and subsequently accumulated with age. The common 4977 nucleotide pair (np) deletion (mtDNA4977) reached a maximum of 0.007%, with the mtDNA7436 and mtDNA10,422 deletions appearing at the same time. In hearts deprived of mitochondrial substrates due to coronary artery disease, the level of the mtDNA4977 deletion was elevated 7-220-fold over age-matched controls, with the mtDNA7436 and mtDNA10,422 deletions increasing in parallel. This cumulative mtDNA damage was associated with a compensatory 3.5-fold induction of nuclear OXPHOS gene mRNA and regions of ischemic hearts subjected to the greatest work load (left ventricle) showed the greatest accumulation of mtDNA damage and OXPHOS gene induction. These observations support the hypothesis that mtDNA damage does accumulate with age and indicates that respiratory stress greatly elevates mitochondrial damage.