Hypoxemia is associated with mitochondrial DNA damage and gene induction. Implications for cardiac disease.
Hypoxemia is associated with mitochondrial DNA damage and gene induction. Implications for cardiac disease.
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DOI：
10.1001/jama.1991.03470130092035
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发表时间：
1991-10
期刊：
影响因子：
--
通讯作者：
M. Corral‐Debrinski;G. Stepien;J. Shoffner;M. Lott;K. Kanter;D. Wallace
中科院分区：
文献类型：
--
作者：
M. Corral‐Debrinski;G. Stepien;J. Shoffner;M. Lott;K. Kanter;D. Wallace
目的：低氧血症或其他原因引起的氧化磷酸化（OXPHOS）缺陷被认为会增加氧自由基的产生，损伤线粒体DNA（mtDNA），减少三磷酸腺苷的合成，导致代偿性OXPHOS基因诱导。因此，我们研究了正常和缺血性心脏以及其他形式的心脏病中mtDNA损伤和OXPHOS转录物的水平。设计--从心脏中提取DNA，以mtDNA常见的4977碱基对缺失水平作为mtDNA损伤的指标。从心脏提取总RNA并分析OXPHOS转录水平。结果：在对照组中，4977个碱基对的mtDNA缺失出现在40岁时，最大缺失率为0.0035%。在缺血性心脏中发现了更高的水平（0.02%至0.85%），以及10例其他类型心脏病中的3例（0.017%至0.16%）。在所有患病的心脏中，OXPHOS转录本增加。结论--缺血心脏线粒体DNA损伤和OXPHOS基因表达增加，提示线粒体DNA损伤与OXPHOS缺乏有关。氧化磷酸化缺陷也可能在其他形式的心脏疾病中发挥作用。
OBJECTIVE --Oxidative phosphorylation (OXPHOS) deficiency due to hypoxemia or other causes was hypothesized to increase oxygen radical generation, damage mitochondrial DNA (mtDNA), and reduce adenosine triphosphate synthesis, resulting in compensatory OXPHOS gene induction. Therefore, we investigated the levels of mtDNA damage and OXPHOS transcripts in normal and ischemic hearts, and then in other forms of heart disease. DESIGN --DNA was extracted from the heart and the levels of the common 4977 base pair mtDNA deletion were quantitated as an index for mtDNA damage. Total RNA was extracted from hearts and analyzed for OXPHOS transcript levels. RESULTS --In control hearts, the 4977 base pair mtDNA deletion appeared at age 40 years and reached a maximum deletion of 0.0035%. Much higher levels were found in ischemic hearts (0.02% to 0.85%), as well as in three of 10 cases with other types of heart disease (0.017% to 0.16%). The OXPHOS transcripts were increased in all diseased hearts. CONCLUSION --Ischemic hearts have increased mtDNA damage and OXPHOS gene expression, suggesting that mtDNA damage is associated with OXPHOS deficiency. Oxidative phosphorylation defects may also play a role in some other forms of cardiac disease.