Compartmentalized regulation of NAD+ by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblast

被引：13

作者：

Zhao, Shuai ^{[1
,2
]}

Hong, Yun ^{[1
,2
]}

Liang, Yue-yue ^{[1
,2
]}

Li, Xiao-lu ^{[1
,2
]}

Shen, Jiang-chuan ^{[3
]}

Sun, Cong-cong ^{[1
,4
]}

Chu, Ling-luo ^{[5
]}

Hu, Jie ^{[1
]}

Wang, Hua ^{[1
]}

Xu, De-xiang ^{[1
]}

Zhang, Shi-chen ^{[1
,6
]}

Xu, Dou-dou ^{[7
]}

Xu, Tao ^{[1
,2
]}

Zhao, Ling-li ^{[1
]}

机构：

[1] Anhui Med Univ, Key Lab Environm Toxicol, Sch Publ Hlth, Dept Toxicol,Anhui Higher Educ Inst,Anhui Prov Key, 81 Meishan Rd, Hefei 230032, Peoples R China

[2] Hefei Univ, Sch Biol Food & Environm, Hefei 230601, Peoples R China

[3] Indiana Univ, Dept Mol & Cellular Biochem, Bloomington, IN 47405 USA

[4] Fudan Univ, Ctr Water & Hlth, Sch Publ Hlth, Key Lab Publ Hlth Safety,Minist Educ,Dept Environm, Shanghai 200032, Peoples R China

[5] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[6] Anhui Med Coll, Sch Publ Hlth & Hlth Management, 632 Furong Rd, Hefei 230601, Anhui, Peoples R China

[7] Anhui Med Univ, Dept Pediat, Affiliated Hosp 1, Hefei 230022, Anhui, Peoples R China

来源：

REDOX BIOLOGY | 2022年 / 55卷

基金：

中国国家自然科学基金;

关键词：

Di (2-ethyl-hexyl) phthalate; Nicotinamide adenine dinucleotide; ATP; DNA damage; Placental development; OXIDATIVE STRESS; NITRIC-OXIDE; MITOCHONDRIAL-FUNCTION; REPAIR; EXPOSURE; CELLS; LONGEVITY; RESPONSES; MODULATION; ACTIVATION;

D O I：

10.1016/j.redox.2022.102414

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页数：15

共 99 条

[81] Circular RNA hsa_circ_0000848 Promotes Trophoblast Cell Migration and Invasion and Inhibits Cell Apoptosis by Sponging hsa-miR-6768-5p [J].