PARP-1/PAR Activity in Cultured Human Lens Epithelial Cells Exposed to Two Levels of UVB Light.

PARP-1/PAR Activity in Cultured Human Lens Epithelial Cells Exposed to Two Levels of UVB Light.
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暴露于两级 UVB 光的培养人晶状体上皮细胞中的 PARP-1/PAR 活性。

DOI:
10.1111/php.12814
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发表时间:
2018-01
影响因子:
3.3
通讯作者:
Giblin FJ
Giblin FJ
中科院分区:
生物学3区
文献类型:
--
作者:
Cencer CS;Chintala SK;Townsend TJ;Feldmann DP;Awrow MA;Putris NA;Geno ME;Donovan MG;Giblin FJ

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本研究探讨了暴露于两种水平的UVB光(312 nm峰值波长),0.014和0.14 J/cm 2(分别为“低”和“高”剂量)的培养人透镜上皮细胞中聚(ADP-核糖)聚合酶-1(PARP-1)的激活。在低剂量下,PARP-1和聚(ADP-核糖)(PAR)聚合物迅速修复DNA链断裂,随后对细胞形态或活力没有重大影响。然而,在高UVB剂量后,90分钟后出现了戏剧性的PARP-1活化的第二阶段,其中包括DNA链断裂的突然再现,线粒体和细胞核内活性氧(ROS)形成的爆发,PAR从细胞核易位到线粒体,以及24小时后发生的70%的细胞活力的最终损失。这些结果为PARP-1在保护人类透镜上皮细胞免受低水平UVB光的伤害方面的重要作用提供了证据,并且可能参与了暴露于毒性水平辐射后触发细胞死亡。将培养的人透镜上皮细胞暴露于0.14 J/cm 2的UVB光2.5分钟后5分钟,在细胞核中产生聚(ADP-核糖)(PAR)聚合物以帮助DNA的修复,然后聚合物消失。令人惊讶的是,暴露90分钟后,PAR聚合物再次产生,但这次聚合物似乎从细胞核中迁移到细胞线粒体中,可能引发细胞死亡。
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/cm2 (“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 both within 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 hrs. 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. Five minutes after a 2.5 minute exposure of cultured human lens epithelial cells to 0.14 J/cm2 of UVB light, poly (ADP-ribose) (PAR) polymers were produced in the cell nucleus to assist in the repair of DNA, and the polymers then disappeared. Surprisingly, 90 minutes after the exposure, PAR polymers were produced once again, but this time the polymers appeared to travel out of the nucleus to the cell mitochondria, possibly to initiate cell death.
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