Compartmentalized regulation of NAD+ by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblast
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722001860 |
| _version_ | 1811215920370024448 |
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| author | Shuai Zhao Yun Hong Yue-yue Liang Xiao-lu Li Jiang-chuan Shen Cong-cong Sun Ling-luo Chu Jie Hu Hua Wang De-xiang Xu Shi-chen Zhang Dou-dou Xu Tao Xu Ling-li Zhao |
| author_facet | Shuai Zhao Yun Hong Yue-yue Liang Xiao-lu Li Jiang-chuan Shen Cong-cong Sun Ling-luo Chu Jie Hu Hua Wang De-xiang Xu Shi-chen Zhang Dou-dou Xu Tao Xu Ling-li Zhao |
| author_sort | Shuai Zhao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T06:31:26Z |
| format | Article |
| id | doaj.art-6d50f840466f4023a2604073af4e8c25 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-12T06:31:26Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-6d50f840466f4023a2604073af4e8c252022-12-22T03:44:00ZengElsevierRedox Biology2213-23172022-09-0155102414Compartmentalized regulation of NAD+ by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblastShuai Zhao0Yun Hong1Yue-yue Liang2Xiao-lu Li3Jiang-chuan Shen4Cong-cong Sun5Ling-luo Chu6Jie Hu7Hua Wang8De-xiang Xu9Shi-chen Zhang10Dou-dou Xu11Tao Xu12Ling-li Zhao13Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, China; School of Biology, Food and Environment, Hefei University, Hefei, 230601, ChinaKey Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, China; School of Biology, Food and Environment, Hefei University, Hefei, 230601, ChinaKey Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, China; School of Biology, Food and Environment, Hefei University, Hefei, 230601, ChinaKey Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, China; School of Biology, Food and Environment, Hefei University, Hefei, 230601, ChinaDepartment of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, 47405, USAKey Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, China; Key Laboratory of the Public Health Safety, Ministry of Education, Department of Environmental Health, School of Public Health / Center for Water and Health, School of Public Health, Fudan University, Shanghai, 200032, ChinaDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, 02138, USAKey Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, ChinaKey Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, ChinaKey Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, ChinaSchool of Public Health and Health Management, Anhui Medical College, No 632 Furong Road, Hefei, Anhui, 230601, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, ChinaDepartment of Pediatrics, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, ChinaSchool of Biology, Food and Environment, Hefei University, Hefei, 230601, China; Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, China; Corresponding author. School of Biology, Food and Environment, Hefei University, Hefei, 230601, China.Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, China; Corresponding author. Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Department of Toxicology, Anhui Provincial Key Laboratory of Population Health and Aristogenics, MOE Key Laboratory of Population Health Across Life Cycle, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, China.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.http://www.sciencedirect.com/science/article/pii/S2213231722001860Di (2-ethyl-hexyl) phthalateNicotinamide adenine dinucleotideATPDNA damagePlacental development |
| spellingShingle | Shuai Zhao Yun Hong Yue-yue Liang Xiao-lu Li Jiang-chuan Shen Cong-cong Sun Ling-luo Chu Jie Hu Hua Wang De-xiang Xu Shi-chen Zhang Dou-dou Xu Tao Xu Ling-li Zhao Compartmentalized regulation of NAD+ by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblast Redox Biology Di (2-ethyl-hexyl) phthalate Nicotinamide adenine dinucleotide ATP DNA damage Placental development |
| title | Compartmentalized regulation of NAD+ by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblast |
| title_full | Compartmentalized regulation of NAD+ by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblast |
| title_fullStr | Compartmentalized regulation of NAD+ by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblast |
| title_full_unstemmed | Compartmentalized regulation of NAD+ by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblast |
| title_short | Compartmentalized regulation of NAD+ by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblast |
| title_sort | compartmentalized regulation of nad by di 2 ethyl hexyl phthalate induces dna damage in placental trophoblast |
| topic | Di (2-ethyl-hexyl) phthalate Nicotinamide adenine dinucleotide ATP DNA damage Placental development |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722001860 |
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