title: Activation of Trim17 by PPARγ is involved in di(2-ethylhexyl) phthalate (DEHP)-induced apoptosis on Neuro-2a cells.
abstract: Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in plastics. Its reproductive toxicity and teratogenic effects are well known. DEHP can cause liver damage and peroxisome proliferation, as well as carcinogenesis. Animal study has shown that DEHP causes neurodegeneration in rat brain. Prenatal exposure to DEHP disrupts brain development and decreases brain weight in rats. But its mechanism of action in the brain is not clear. This study used a neuroblastoma cell line, Neuro-2a cells, to investigate the toxic effect of DEHP. The results revealed that DEHP inhibits cell proliferation, activate caspase-3, induce apoptosis in a dose and time dependent manner, and activate expression of the PPARγ and Trim17 protein. Administration of the PPARγ agonist (troglitazone) enhanced DEHP-induced Trim17 protein expression and this enhancement could be reversed by the PPARγ antagonist (GW9662). These results suggest that DEHP activates the Trim17 protein via PPARγ leading to cleavage pro-caspase-3 and apoptosis. This finding may account for the central nervous system toxicity of DEHP and implies DEHP can impair fetal brain development.
authors.affiliation: Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Chuang-Hao
authors.initials: CH
authors.lastname: Lin
authors.forename: Tsan-Ju
authors.initials: TJ
authors.lastname: Chen
authors.forename: Shun-Sheng
authors.initials: SS
authors.lastname: Chen
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Hsiao
authors.forename: Rei-Cheng
authors.initials: RC
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3 / Q000032:analysis; D053181:Caspase 8 / Q000032:analysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D051379:Mice; D047495:PPAR gamma / Q000502:physiology*; D010968:Plasticizers / Q000633:toxicity*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D047495:PPAR gamma; D010968:Plasticizers; D000070584:Tripartite Motif Proteins; D004051:Diethylhexyl Phthalate; C485451:Trim17 protein, mouse; D044767:Ubiquitin-Protein Ligases; D053148:Caspase 3; D053181:Caspase 8