Eye Research Institute, Oakland University, Rochester, MI.
Photochem Photobiol. 2018 Jan;94(1):126-138. doi: 10.1111/php.12814. Epub 2017 Sep 15.
This study investigated poly(ADP-ribose) polymerase-1 (PARP-1) activation in cultured human lens epithelial cells exposed to two levels of UVB light (312 nm peak wavelength), 0.014 and 0.14 J cm ("low" and "high" dose, respectively). At the low dose, PARP-1 and poly(ADP-ribose) (PAR) polymers acted to repair DNA strand breaks rapidly with no subsequent major effects on either cell morphology or viability. However, following the high UVB dose, there was a dramatic second phase of PARP-1 activation, 90 min later, which included a sudden reappearance of DNA strand breaks, bursts of reactive oxygen species (ROS) formation within both the mitochondria and nucleus, a translocation of PAR from the nucleus to the mitochondria and an ultimate 70% loss of cell viability occurring after 24 h. The results provide evidence for an important role for PARP-1 in protecting the human lens epithelium against low levels of UVB light, and possibly participating in the triggering of cell death following exposure to toxic levels of radiation.
本研究调查了暴露于两种水平的 UVB 光(312nm 峰值波长),0.014 和 0.14 J cm 的培养的人晶状体上皮细胞中的聚(ADP-核糖)聚合酶 1(PARP-1)激活。在低剂量下,PARP-1 和聚(ADP-核糖)(PAR)聚合物迅速修复 DNA 链断裂,对细胞形态或活力没有后续的重大影响。然而,在高剂量的 UVB 之后,PARP-1 的激活出现了戏剧性的第二阶段,90 分钟后,包括 DNA 链断裂的突然再次出现、线粒体和核内活性氧(ROS)形成的爆发、PAR 从核到线粒体的易位以及 24 小时后细胞活力最终丧失 70%。研究结果为 PARP-1 在保护人晶状体上皮细胞免受低水平 UVB 光的损伤,以及在暴露于有毒水平辐射后参与触发细胞死亡方面提供了证据。