Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Republic of Korea.
Free Radic Res. 2012 Jan;46(1):21-9. doi: 10.3109/10715762.2011.636042. Epub 2011 Nov 22.
Mitochondrial adenine nucleotide translocator (ANT) plays important roles in the regulation of mitochondrial permeability transition and cell bioenergetics. The mouse has three ANT isoforms (1, 2 and 4) showing tissue-specific expression patterns. Although ANT1 is known to have a pro-apoptotic property, the specific functions of ANT2 have not been well determined. In the present study, ANT2 expression was significantly lower in the aged rat liver and in a liver fibrosis model. To explore the protective role of ANT2 in the liver, we established a hepa1c1c7 cell line overexpressing ANT2. Overexpression of ANT2 caused hepa1c1c7 cells to be more resistant to oxidative stress, and mitochondrial membrane potential (MMP, ∆Ψm) was relatively intact in ANT2-overexpressing cells under oxidative stress. In addition, ANT2 was found to increase ATP production by influencing mitochondrial bioenergetics. These results imply that the hepatoprotective effect of ANT2 is due to the stabilization of MMP and enhanced ATP production, and thus, maintaining ANT2 levels in the liver might be important to enhance resistance to aging and oxidative stress.
线粒体腺嘌呤核苷酸转运蛋白（ANT）在调节线粒体通透性转换和细胞生物能量学方面发挥着重要作用。小鼠有三种 ANT 同工型（1、2 和 4），表现出组织特异性表达模式。尽管已知 ANT1 具有促凋亡特性，但 ANT2 的具体功能尚未得到很好的确定。在本研究中，衰老大鼠肝脏和肝纤维化模型中的 ANT2 表达显著降低。为了探索 ANT2 在肝脏中的保护作用，我们建立了过表达 ANT2 的 hepa1c1c7 细胞系。ANT2 的过表达使 hepa1c1c7 细胞对氧化应激更具抗性，并且在氧化应激下，ANT2 过表达细胞中的线粒体膜电位（MMP，∆Ψm）相对完整。此外，发现 ANT2 通过影响线粒体生物能量学来增加 ATP 的产生。这些结果表明，ANT2 的肝保护作用是由于 MMP 的稳定和 ATP 产生的增强，因此，维持肝脏中的 ANT2 水平对于增强对衰老和氧化应激的抵抗力可能很重要。
