Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, China.
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 120-750, South Korea.
Free Radic Biol Med. 2021 Jan;162:141-148. doi: 10.1016/j.freeradbiomed.2020.11.022. Epub 2020 Nov 26.
Hepatic steatosis and subsequent fatty liver disease are developed in response to alcohol consumption. Reactive oxygen species (ROS) are thought to play an important role in the alcoholic fatty liver disease (AFLD). However, the molecular targets of ROS and the underlying cellular mechanisms are unknown. Here, we investigate roles of peroxiredoxin III and redox regulation of phosphatase and tension homolog deleted on chromosome 10 (PTEN) in the alcoholic fatty liver. Alcohol-induced mitochondrial oxidative stress was found to contribute to reversible oxidation of PTEN, which results in Akt and MAPK hyperactivation with elevated levels of the lipogenesis regulators SREBP1c and PPARγ. Moreover, mitochondrial peroxiredoxin III was found to have antagonistic effects on lipogenesis via the redox regulation of PTEN by removing ROS, upon alcohol exposure. This study demonstrated that redox regulation of PTEN and peroxiredoxin III play crucial roles in the development of AFLD.
酒精性脂肪肝是由于饮酒而导致的肝脏脂肪变性和随后的脂肪性肝病。活性氧（ROS）被认为在酒精性脂肪肝（AFLD）中发挥重要作用。然而，ROS 的分子靶点和潜在的细胞机制尚不清楚。在这里，我们研究了过氧化物酶 III 和磷酸酶和张力同源物缺失的 10 号染色体（PTEN）的氧化还原调节在酒精性脂肪肝中的作用。发现酒精诱导的线粒体氧化应激导致 PTEN 的可逆氧化，从而导致 Akt 和 MAPK 的过度激活，脂生成调节剂 SREBP1c 和 PPARγ 的水平升高。此外，在线粒体过氧化物酶 III 的情况下，发现通过去除 ROS 对 PTEN 的氧化还原调节，具有拮抗脂生成的作用，酒精暴露。这项研究表明，PTEN 和过氧化物酶 III 的氧化还原调节在 AFLD 的发展中起着至关重要的作用。
