Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients
Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients
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DOI：
10.1016/s0168-8278(97)80286-3
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发表时间：
1997-07-01
影响因子：
25.7
通讯作者：
Pessayre, D
中科院分区：
文献类型：
--
作者：
Mansouri, A;Fromenty, B;Pessayre, D
背景/目标：在患有微泡性脂肪变性的酒精患者的肝线粒体DNA中检测到4977个碱基对缺失，这是一种归因于线粒体β-氧化受损的病变。然而，在先前的研究中仅发现了一个缺失，并且无法确定该缺失是预先存在的还是获得性的。酒精滥用增加了肝线粒体中活性氧的形成。如果这种影响加速了线粒体DNA的氧化老化，其他几个突变将expected.Methods：从核苷酸8167到核苷酸14246延伸的线粒体DNA区域进行了筛选，在58个酒精患者和67个年龄匹配的非酒精对照的存在下，大的线粒体DNA缺失。对肝脏DNA进行聚合酶链反应，分别扩增非缺失和缺失的线粒体DNA，并对线粒体DNA缺失的边界进行测序。只有3%的非酒精性对照携带线粒体DNA缺失，而所有酒精性患者中的24%和13名患有微泡性脂肪变性的酒精性患者中的85%表现出单个或多个4977，5385、5039和5556碱基对线粒体DNA缺失。然而，在13例因其他原因引起的微泡性脂肪变性患者中，未观察到缺失（S）。结论：在酒精性微泡性脂肪变性患者中观察到不同的线粒体DNA重排。我们认为，酒精滥用导致线粒体DNA的过早氧化老化。假设，线粒体成分（DNA，蛋白质和脂质）的氧化损伤可能有利于微泡脂肪沉积。
Background/Aims: A 4977-base pair deletion has been detected in the hepatic mitochondrial DNA of alcoholic patients with microvesicular steatosis, a lesion ascribed to impaired mitochondrial beta-oxidation. However, only a single deletion had been looked for in this previous study, and it could not be determined whether the deletion was preexisting or acquired, Alcohol abuse increases the formation of reactive oxygen species in hepatic mitochondria. If this effect accelerates the oxidative aging of mitochondrial DNA, several other mutations would be expected.Methods: The mtDNA region extending from nucleotide 8167 to nucleotide 14246 was screened for the presence of large mitochondrial DNA deletions in 58 alcoholic patients and 67 age-matched non-alcoholic controls. Hepatic DNA was subjected to polymerase chain reactions that amplified non-deleted and deleted mitochondrial DNA, respectively, and the boundaries of the mitochondrial DNA deletions were sequenced.Results: Only 3% of the non-alcoholic controls carried a mitochondrial DNA deletion, whereas 24% of all alcoholic patients and 85% of the 13 alcoholic patients with microvesicular steatosis exhibited either single or multiple 4977, 5385, 5039 and 5556-base pair mitochondrial DNA deletions. No deletion(s) were observed, however, in 13 patients with microvesicular steatosis due to other causes.Conclusions: Diverse mitochondrial DNA rearrangements are observed in alcoholic patients with micro vesicular steatosis. We suggest that alcohol abuse leads to premature oxidative aging of mitochondrial DNA. Hypothetically, oxidative damage to mitochondrial constituents (DNA, proteins and lipids) may favor microvesicular fat deposition.