NAD+激酶
PARP1
DNA损伤
线粒体
线粒体DNA
DNA修复
邻苯二甲酸盐
滋养层
DNA
化学
生物
细胞生物学
生物化学
胎盘
聚ADP核糖聚合酶
酶
胎儿
遗传学
基因
怀孕
聚合酶
有机化学
作者
Shuai Zhao,Yun Soo Hong,Yue-yue Liang,Xiaolu Li,Jiang-chuan Shen,Congcong Sun,Lingluo Chu,J. F. Hu,Hua Wang,De-Xiang Xu,Shichen Zhang,Dianna Xu,Tao Xu,Lingli Zhao
出处
期刊:Redox biology
[Elsevier]
日期:2022-09-01
卷期号:55: 102414-102414
被引量:2
标识
DOI:10.1016/j.redox.2022.102414
摘要
Di (2-ethyl-hexyl) phthalate (DEHP) is a wildly used plasticizer. Maternal exposure to DEHP during pregnancy blocks the placental cell cycle at the G2/M phase by reducing the efficiency of the DNA repair pathways and affects the health of offsprings. However, the mechanism by which DEHP inhibits the repair of DNA damage remains unclear. In this study, we demonstrated that DEHP inhibits DNA damage repair by reducing the activity of the DNA repair factor recruitment molecule PARP1. NAD+ and ATP are two substrates necessary for PARP1 activity. DEHP abated NAD+ in the nucleus by reducing the level of NAD+ synthase NMNAT1 and elevated NAD+ in the mitochondrial by promoting synthesis. Furthermore, DEHP destroyed the mitochondrial respiratory chain, affected the structure and quantity of mitochondria, and decreased ATP production. Therefore, DEHP inhibits PARP1 activity by reducing the amount of NAD+ and ATP, which hinders the DNA damage repair pathways. The supplement of NAD+ precursor NAM can partially rescue the DNA and mitochondria damage. It provides a new idea for the prevention of health problems of offsprings caused by DEHP injury to the placenta.
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