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

ABSTRACT: 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, aff

SUBMITTER: Zhao S 

PROVIDER: S-EPMC9356100 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature