Abstract
Persistent organochlorine pollutants (POPs) gradually accumulate in the human organism due to their presence in the environment. Some studies have described a correlation between the level of POPs in the human body and the incidence of diabetes, but we know little about the direct effect of POPs on pancreatic beta-cells. We exposed pancreatic beta-cells INS1E to non-lethal concentrations of p,p′-DDT (1,1′-(2,2,2-Trichloroethane-1,1-diyl)bis(4-chlorobenzene)) and p,p′-DDE (1,1′-(2,2-dichloroethene-1,1-diyl)bis(4-chlorobenzene)) for 1 month, and assessed changes in protein expression and the intracellular insulin level. 2-D electrophoresis revealed 6 proteins with changed expression in cells exposed to p,p′-DDT or p,p′-DDE. One of the detected proteins – vitamin D-binding protein (VDBP) – was upregulated in both cells exposed to p,p′-DDT, and cells exposed to p,p′-DDE. Both exposures to pollutants reduced the intracellular level of insulin mRNA, proinsulin, and insulin monomer; p,p′-DDT also slightly reduced the level of hexameric insulin. Overexpression of VDBP caused by the stable transfection of beta-cells with the gene for VDBP decreased both the proinsulin and hexameric insulin level in beta-cells similarly to the reduction detected in cells exposed to p,p′-DDT. Our data suggest that in the cells exposed to p,p′-DDT and p,p′-DDE, the increased VDBP protein level decreased the proinsulin expression in an unknown mechanism.
Highlights
Persistent organochlorine pollutants (POPs) gradually accumulate in the human organism due to their presence in the environment
Exposure to p,p′-DDT changed the expression of six spots. Mass spectrometry identified these spots as:(1) actin with expression decreased to 39% of the control, (2) mortalin/GRP75 (75 kDa glucose-regulated protein; spot T3) with expression decreased to 56% of the control, (3) tubulin beta-5 chain with expression increased to 251% and 188% of the control, (4) annexin A4 with expression increased to 254% of the control, and (5) vitamin D-binding protein (VDBP, spot T2) with expression increased to 327% of the control (Fig. 3, Table 1)
We have shown that a 1-month exposure to a non-lethal dose (10 μM) of p,p′-DDT increased the expression of the vitamin D-binding protein, tubulin beta-5 chain, and annexin A4; and decreased the expression of actin, and mortalin/GRP75 in rat pancreatic beta-cells INS1E
Summary
Persistent organochlorine pollutants (POPs) gradually accumulate in the human organism due to their presence in the environment. We exposed pancreatic beta-cells INS1E to non-lethal concentrations of p,p′-DDT (1,1′-(2,2,2-Trichloroethane-1,1-diyl)bis(4-chlorobenzene)) and p,p′-DDE (1,1′-(2,2-dichloroethene-1,1diyl)bis(4-chlorobenzene)) for 1 month, and assessed changes in protein expression and the intracellular insulin level. One of the detected proteins – vitamin D-binding protein (VDBP) – was upregulated in both cells exposed to p,p′-DDT, and cells exposed to p,p′-DDE Both exposures to pollutants reduced the intracellular level of insulin mRNA, proinsulin, and insulin monomer; p,p′-DDT slightly reduced the level of hexameric insulin. Our data suggest that in the cells exposed to p,p′-DDT and p,p′-DDE, the increased VDBP protein level decreased the proinsulin expression in an unknown mechanism. ER stress can result in the full recovery of pancreatic beta cells or their apoptosis[34]
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