当前位置: X-MOL 学术Chem. Res. Toxicol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Probing the Hidden Role of Mitochondrial DNA Damage and Dysfunction in the Etiology of Aristolochic Acid Nephropathy
Chemical Research in Toxicology ( IF 4.1 ) Pub Date : 2021-07-13 , DOI: 10.1021/acs.chemrestox.1c00175
Wan Chan 1 , Yat-Hing Ham 1
Affiliation  

Aristolochic acid nephropathy (AAN) is a unique type of progressive renal interstitial fibrotic disease caused by prolonged exposure to aristolochic acids (AAs) through AA-containing herbal medicines or AA-tainted food. Despite decades of research and affecting millions of people around the world, the pathophysiology of AAN remains incompletely understood. In this study, we tested the potential causative role of mitochondrial dysfunction in AAN development. Our findings revealed AA exposure induces an exposure concentration and duration dependent lowering of adenosine triphosphate in both cultured human kidney and liver cells, highlighting an AA exposure effect on mitochondrial energy production in the kidney and liver, which both are highly metabolically active and energy-demanding organs. Analysis with liquid chromatography–tandem mass spectrometry coupled with stable isotope dilution method detected high levels of mutagenic 8-oxo-2′-deoxyguanosine and 7-(deoxyadenosine-N6-yl)-aristolactam adduct on mitochondrial DNA isolated from AA-treated cells, unmasking a potentially important causative, but previously unknown role of mitochondrial DNA mutation in the pathophysiology of AAN development.

中文翻译:

探讨线粒体 DNA 损伤和功能障碍在马兜铃酸肾病病因学中的隐藏作用

马兜铃酸肾病 (AAN) 是一种独特的进行性肾间质纤维化疾病,由通过含 AA 的草药或受 AA 污染的食物长期接触马兜铃酸 (AA) 引起。尽管进行了数十年的研究并影响了全世界数百万人,但 AAN 的病理生理学仍未完全了解。在这项研究中,我们测试了线粒体功能障碍在 AAN 发展中的潜在致病作用。我们的研究结果表明,AA 暴露会导致培养的人肾细胞和肝细胞中三磷酸腺苷的暴露浓度和持续时间依赖性降低,突出了 AA 暴露对肾脏和肝脏线粒体能量产生的影响,这两者都具有高度的代谢活性和能量需求器官。从 AA 处理的细胞中分离出的线粒体 DNA 上的N 6 -yl)-马里内酰胺加合物,揭示了线粒体 DNA 突变在 AAN 发展的病理生理学中的潜在重要致病作用,但以前未知的作用。
更新日期:2021-08-16
down
wechat
bug