Abstract
Many compounds have the potential to harm pancreatic beta-cells; organochlorine pollutants belong to those compounds. In this work, we aimed to find markers of acute toxicity of p,p'-DDT exposure among proteins expressed in NES2Y human pancreatic beta-cells employing 2-D electrophoresis. We exposed NES2Y cells to a high concentration (150 μM, LC96 after 72 hours) of p,p'-DDT for 24 and 30 hours and determined proteins with changed expression using 2-D electrophoresis. We have found 22 proteins that changed their expression. They included proteins involved in ER stress (GRP78, and endoplasmin), mitochondrial proteins (GRP75, ECHM, IDH3A, NDUS1, and NDUS3), proteins involved in the maintenance of the cell morphology (EFHD2, TCPA, NDRG1, and ezrin), and some other proteins (HNRPF, HNRH1, K2C8, vimentin, PBDC1, EF2, PCNA, biliverdin reductase, G3BP1, FRIL, and HSP27). The proteins we have identified may serve as indicators of p,p'-DDT toxicity in beta-cells in future studies, including long-term exposure to environmentally relevant concentrations.
Highlights
Many compounds have the potential to harm pancreatic beta-cells and disrupt glucose homeostasis in the human organism [1]
We found four mitochondrial proteins downregulated in pancreatic beta-cells after exposure to p,p‘-DDT: ECHM, isocitrate dehydrogenase [NAD] 3 subunit alpha (IDH3A), NDUS1, and NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUS3)
We aimed to find markers of acute toxicity of a high concentration of p,p‘-DDT in NES2Y human pancreatic beta-cells employing 2D electrophoresis
Summary
Many compounds have the potential to harm pancreatic beta-cells and disrupt glucose homeostasis in the human organism [1] Such compounds include pharmaceuticals like pentamidine [2], or fluoxetine (SSRI antidepressant) [3] or saturated fatty acids palmitate [4], or stearate [5], and potentially organochlorine pollutants, such as the now-banned pesticide DDT [6, 7]. Epidemiologic studies [15,16,17,18] showed a correlation between DDT in the human organism and the incidence of diabetes mellitus. They did not specify if DDT affected insulin production by pancreatic beta-cells or insulin signaling in target tissues [7, 19, 20]
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