title: The role of oxidative stress in DNA damage in pancreatic β cells induced by di-(2-ethylhexyl) phthalate.
abstract: Di(2-ethyhexyl) phthalate (DEHP) is commonly used as a plasticizer, which loosely binds to plastic materials and easily leaches out of these products and enters into the environment. Exposure to DEHP can impair pancreatic beta cells (INS-1 cells)function, which is associated with Insulin Resistance (IR) and type 2 diabetes. However, the mechanism of how DEHP leads to Insulin Resistance is unknown. Our results showed that the cell viability of INS-1 cells exposed to DEHP (0-1600 μM) were decreased in a concentration-dependent manner. DEHP caused significant increases of DNA migration and oxidative damage in INS-1 cells. Lysosomal membrane permeability was increased and mitochondrial membrane potential was reduced after INS-1 cells treated with DEHP. DEHP was also shown to induce ROS production and cause GSH depletion in INS-1 cells. DEHP brought a significant decrease in super oxide dismutase (SOD) and led to accumulation of malondialdehyde (MDA) in the INS-1 cells. DEHP increased significantly the expression of P53 and ATM gene of INS-1 cell at high dose levels. Simultaneously, Pyrroloquinoline Quinone (PQQ), an antioxidant, and alcohol were used in the study to determine their effects on DEHP-induced INS-1 cells damage. PQQ could protect the INS-1 cells from the damage induced by DEHP to some extent, while alcohol aggravated the toxic effects of DEHP. These results indicate that DEHP-mediated INS-1 cell dysfunction through a lysosomal-mitochondrial pathway, involving oxidative stress and p53 and ATM activation.
authors.affiliation: Department of Nutrition and Food Safety, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: She
authors.affiliation: Preventive Medicine Laboratory, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Safety, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Nutrition and Food Safety, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Heming
authors.initials: H
authors.lastname: Zuo
authors.affiliation: Department of Nutrition and Food Safety, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Department of Occupational and Environmental Health, College of Public Health, Dalian Medical University, No. 9 West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Xiance
authors.initials: X
authors.lastname: Sun
authors.affiliation: Preventive Medicine Laboratory, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Qiujuan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Preventive Medicine Laboratory, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Geng
authors.affiliation: Department of Nutrition and Food Safety, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, The Affiliated Zhong Shan Hospital of Dalian University, Dalian 116001, Liaoning, PR China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Safety, College of Public Health, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China; Natural Products Engineering Technology Center, Dalian Medical University, No.9, West Segment of South Lvshun Road, Dalian 116044, Liaoning, PR China. Electronic address: food@dlmedu.edu.cn.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D007425:Intracellular Membranes / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress; D010539:Permeability; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D008315:Malondialdehyde; D004247:DNA; D004051:Diethylhexyl Phthalate; D013482:Superoxide Dismutase; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: Di(2-ethyhexyl) phthalate; Insulin Resistance; Oxidative DNA damage; Oxidative stress; PQQ