title: Effect of prolonged exposure to sublethal concentrations of DDT and DDE on protein expression in human pancreatic beta cells.
abstract: Pollution of the environment represents one of less explored potential reasons for the worldwide epidemic of type 2 diabetes. One of the most prevalent organochlorine pollutants remains the pesticide DDT and its degradation product DDE. Despite some epidemiologic correlations between levels of DDT and DDE in human organism and the prevalence of diabetes, there is almost no information about the exact targets of these compounds inside pancreatic beta cells. To detect functional areas of pancreatic beta cells that could be affected by exposure to DDT and DDE, we analyzed changes in protein expression in the NES2Y human pancreatic beta cell line exposed to three sublethal concentrations (0.1 μM, 1 μM, 10 μM) of DDT and DDE for 1 month. Protein separation and identification was achieved using high-resolution 2D-electrophoresis, computer analysis and mass spectrometry. With these techniques, four proteins were found downregulated after exposure to 10 μM DDT: three cytoskeletal proteins (cytokeratin 8, cytokeratin 18 and actin) and one protein involved in glycolysis (alpha-enolase). Two proteins were downregulated after exposure to 10 μM DDE: cytokeratin 18 and heterogenous nuclear ribonucleoprotein H1 (HNRH1). These changes correlate with previously described effects of other stress conditions (e.g. exposure to palmitate, hyperglycemia, imidazoline derivative, and cytokines) on protein expression in pancreatic beta cells. We conclude that cytoskeletal proteins and their processing, glucose metabolism, and mRNA processing may represent targets affected by exposure to conditions hostile to pancreatic beta cells, including exposure to DDT and DDE.
authors.affiliation: Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: nela.pavlikova@lf3.cuni.cz.
authors.forename: Nela
authors.initials: N
authors.lastname: Pavlikova
authors.affiliation: Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Smetana
authors.affiliation: Laboratory of Molecular Structure Characterization, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Halada
authors.affiliation: Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Kovar
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003634:DDT / Q000633:toxicity*; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D004785:Environmental Pollutants; D012333:RNA, Messenger; D003633:Dichlorodiphenyl Dichloroethylene; D003634:DDT; D005947:Glucose
keywords: Alpha-enolase; Cytokeratin; DDT/E; Diabetes; HNRH1