title: Nonylphenol diethoxylate inhibits apoptosis induced in PC12 cells.
abstract: Nonylphenol and short-chain nonylphenol ethoxylates such as NP2EO are present in aquatic environment as wastewater contaminants, and their toxic effects on aquatic species have been reported. Apoptosis has been shown to be induced by serum deprivation or copper treatment. To understand the toxicity of nonylphenol diethoxylate, we investigated the effects of NP2EO on apoptosis induced by serum deprivation and copper by using PC12 cell system. Nonylphenol diethoxylate itself showed no toxicity and recovered cell viability from apoptosis. In addition, nonylphenol diethoxylate decreased DNA fragmentation caused by apoptosis in PC12 cells. This phenomenon was confirmed after treating apoptotic PC12 cells with nonylphenol diethoxylate, whereas the cytochrome c release into the cytosol decreased as compared to that in apoptotic cells not treated with nonylphenol diethoxylates. Furthermore, Bax contents in apoptotic cells were reduced after exposure to nonylphenol diethoxylate. Thus, nonylphenol diethoxylate has the opposite effect on apoptosis in PC12 cells compared to nonylphenol, which enhances apoptosis induced by serum deprivation. The difference in structure of the two compounds is hypothesized to be responsible for this phenomenon. These results indicated that nonylphenol diethoxylate has capability to affect cell differentiation and development and has potentially harmful effect on organisms because of its unexpected impact on apoptosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1389-1398, 2016.
authors.affiliation: Graduate School of Environmental Science, Hokkaido University, Sapporo, 060-0810, Japan.
authors.forename: Chuang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, 453-003, China.|Faculty of Environmental Earth Science, Hokkaido University, Sapporo, 060-0810, Japan.
authors.forename: Yongkun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Graduate School of Environmental Science, Hokkaido University, Sapporo, 060-0810, Japan.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Song
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Graduate School of Environmental Science, Hokkaido University, Sapporo, 060-0810, Japan. kura@ees.hokudai.ac.jp.|Faculty of Environmental Earth Science, Hokkaido University, Sapporo, 060-0810, Japan. kura@ees.hokudai.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kurasaki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D016716:PC12 Cells; D010636:Phenols / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: D010636:Phenols; D019253:Proto-Oncogene Proteins c-bcl-2; D014874:Water Pollutants, Chemical; D051028:bcl-2-Associated X Protein; C025256:nonylphenol; D045304:Cytochromes c
keywords: PC12 cells; apoptosis; cytochrome c; nonylphenol; nonylphenol diethoxylate