Increased expression of uncoupling protein 2 in HepG2 cells attenuates oxidative damage and apoptosis
Increased expression of uncoupling protein 2 in HepG2 cells attenuates oxidative damage and apoptosis
复制标题
DOI：
10.1111/j.1478-3231.2005.01104.x
复制
发表时间：
2005-08-01
影响因子：
6.7
通讯作者：
Hodgson, H
中科院分区：
文献类型：
--
作者：
Collins, P;Jones, C;Hodgson, H
引言：氧化损伤在肝脏疾病的发病机制中起着重要作用。解偶联蛋白（UCPs）可能能够限制活性氧（ROS）的产生并具有细胞保护作用。方法：我们研究了UCP 2在甲萘醌或缺氧/复氧暴露的肝母细胞瘤细胞系中上调的作用。结果如下：脂质和蛋白质氧化增加暴露于ROS的HepG 2细胞，但这种增加在相同条件下过表达UCP 2的细胞中显着降低。在对照HepG 2细胞中，LDH释放响应于缺氧/复氧增加2.5倍，而在UCP 2转染细胞中没有显著增加。缺氧/复氧导致肝脏特异性蛋白分泌减少，在转染细胞中减弱，UCP 2过表达也导致细胞凋亡与未转染对照相比减少66%。结论：这些数据表明，UCP 2可以限制HepG 2细胞中响应于氧化应激的氧化损伤，从而改善细胞功能和抗凋亡。
Introduction: Oxidative damage plays a major part in the pathogenesis of liver disease. Uncoupling proteins (UCPs) may be able to limit the generation of reactive oxygen species (ROS) and be cytoprotective. Methods: We investigated the effect of up-regulation of UCP2 in a hepatoblastoma cell line exposed to menadione or hypoxia/re-oxygenation. Results: Lipid and protein oxidation was increased in HepG2 cells exposed to ROS but this increase was significantly lower in cells over-expressing UCP2 under identical conditions. LDH release increased 2.5-fold in response to hypoxia/re-oxygenation in control HepG2 cells with no significant increase in UCP2 transfected cells. Hypoxia/re-oxygenation resulted in a reduction in liver-specific protein secretion that was attenuated in transfected cells and UCP2 over-expression also resulted in a 66% reduction in apoptosis compared with non-transfected controls. Conclusions: These data suggest that UCP2 can limit oxidative damage in HepG2 cells in response to oxidative stress resulting in improved cell function and resistance to apoptosis.