Decreased Integrity, Content, and Increased Transcript Level of Mitochondrial DNA Are Associated with Keratoconus.
Decreased Integrity, Content, and Increased Transcript Level of Mitochondrial DNA Are Associated with Keratoconus.
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线粒体 DNA 完整性、含量降低和转录水平升高与圆锥角膜相关
DOI：
10.1371/journal.pone.0165580
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Chen P
中科院分区：
文献类型：
--
作者：
Hao XD;Chen ZL;Qu ML;Zhao XW;Li SX;Chen P
氧化应激可能在圆锥角膜（KC）的发病机制中发挥重要作用。线粒体DNA（mtDNA）参与线粒体功能，mtDNA含量、完整性和转录水平可能影响活性氧（ROS）的产生并参与KC的发病机制。我们设计了一项病例对照研究来研究 KC 与 mtDNA 完整性、内容和转录之间的关系。研究人员对来自中国患者的 198 个 KC 角膜和 106 个正常角膜进行了研究。采用实时定量PCR测定线粒体DNA相对含量、线粒体DNA及相关基因的转录水平。使用长延伸PCR来检测mtDNA损伤。通过各自的检测试剂盒测量ROS、线粒体膜电位和ATP，并使用Mito-Tracker Green标记线粒体。 KC角膜的相对mtDNA含量显着低于正常角膜（P = 9.19×10−24），可能是由于线粒体转录因子A（TFAM）基因表达减少（P = 3.26×10−3）。相反，与正常角膜相比，KC角膜中mtDNA基因的转录水平显着增加（NADH脱氢酶亚基1 [ND1]：P = 1.79×10−3；细胞色素c氧化酶亚基1 [COX1]：P = 1.54×10−3；NADH脱氢酶亚基1，[ND6]：P = 4.62×10−3）。后者可能是mtDNA转录相关基因线粒体RNA聚合酶（POLRMT）（P = 2.55×10−4）和转录因子B2线粒体（TFB2M）（P = 7.88×10−5）表达水平增加的结果。与正常角膜相比，KC 角膜的 mtDNA 损伤增加（P = 3.63×10−10），ROS 水平更高，线粒体膜电位和 ATP 水平更低。 mtDNA 完整性、含量降低和转录水平升高与 KC 相关。这些变化可能影响ROS的产生并在KC的发病机制中发挥作用。
Oxidative stress may play an important role in the pathogenesis of keratoconus (KC). Mitochondrial DNA (mtDNA) is involved in mitochondrial function, and the mtDNA content, integrity, and transcript level may affect the generation of reactive oxygen species (ROS) and be involved in the pathogenesis of KC. We designed a case-control study to research the relationship between KC and mtDNA integrity, content and transcription. One-hundred ninety-eight KC corneas and 106 normal corneas from Chinese patients were studied. Quantitative real-time PCR was used to measure the relative mtDNA content, transcript levels of mtDNA and related genes. Long-extension PCR was used to detect mtDNA damage. ROS, mitochondrial membrane potential and ATP were measured by respective assay kit, and Mito-Tracker Green was used to label the mitochondria. The relative mtDNA content of KC corneas was significantly lower than that of normal corneas (P = 9.19×10−24), possibly due to decreased expression of the mitochondrial transcription factor A (TFAM) gene (P = 3.26×10−3). In contrast, the transcript levels of mtDNA genes were significantly increased in KC corneas compared with normal corneas (NADH dehydrogenase subunit 1 [ND1]: P = 1.79×10−3; cytochrome c oxidase subunit 1 [COX1]: P = 1.54×10−3; NADH dehydrogenase subunit 1, [ND6]: P = 4.62×10−3). The latter may be the result of increased expression levels of mtDNA transcription-related genes mitochondrial RNA polymerase (POLRMT) (P = 2.55×10−4) and transcription factor B2 mitochondrial (TFB2M) (P = 7.88×10−5). KC corneas also had increased mtDNA damage (P = 3.63×10−10), higher ROS levels, and lower mitochondrial membrane potential and ATP levels compared with normal corneas. Decreased integrity, content and increased transcript level of mtDNA are associated with KC. These changes may affect the generation of ROS and play a role in the pathogenesis of KC.
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影响因子：
2.8
作者：
GONDHOWIARDJO, TD;VANHAERINGEN, NJ;KIJLSTRA, A
通讯作者：
KIJLSTRA, A
影响因子：
3.3
作者：
Hudson, EK;Hogue, BA;Hansford, RG
通讯作者：
Hansford, RG
影响因子：
3.4
作者：
Hao, Xiao-Dan;Chen, Peng;Xie, Li-Xin
通讯作者：
Xie, Li-Xin
影响因子：
4.4
作者：
Chwa, Marilyn;Atilano, Shari R.;Kenney, M. Cristina
通讯作者：
Kenney, M. Cristina
影响因子：
9.9
作者：
Kim, JY;Hwang, JM;Park, SS
通讯作者：
Park, SS