PCB126-mediated effects on adipocyte energy metabolism and adipokine secretion may result in abnormal glucose uptake in muscle cells

BackgroundExposure to coplanar polychlorinated biphenyls (PCBs) is linked to the development of insulin resistance. Previous studies suggested that PCB126 alters muscle mitochondrial function through an indirect mechanism. Since PCBs are stored in fat, we hypothesized that PCB126 alters adipokine secretion, which in turn affects muscle metabolism.ObjectivesThe objectives of this study were: 1) To study the impacts of PCB126 exposure on adipocyte cytokine/adipokine secretion; 2) To determine whether adipocyte-derived factors alter glucose metabolism and mitochondrial function in myotubes when exposed to PCB126; 3) To determine whether pre-established insulin resistance alters the metabolic responses of adipocytes exposed to PCB126 and the communication between adipocytes and myotubes.Method3T3-L1 adipocytes were exposed to PCB126 (1-100 nM) in two insulin sensitivity conditions (insulin sensitive (IS) and insulin resistant (IR) adipocytes), followed by the measurement of secreted adipokines, mitochondrial function and insulin-stimulated glucose uptake. Communication between adipocytes and myotubes was reproduced by exposing C2C12 or mouse primary myotubes to conditioned medium (CM) derived from IS or IR 3T3-L1 adipocytes exposed to PCB126. Mitochondrial function and insulin-stimulated glucose uptake were then determined in myotubes.ResultsPCB126 significantly increased adipokine (adiponectin, IL-6, MCP-1, TNF-α) secretion and decreased mitochondrial function, glucose uptake and glycolysis in IR but not in IS 3T3-L1 adipocytes. Altered energy metabolism in IR 3T3-L1 adipocytes was linked to decreased phosphorylation of AMP-activated protein kinase (p-AMPK) and increased superoxide dismutase 2 levels, an enzyme involved in reactive oxygen species detoxification. Exposure of myotubes to CM from PCB126-treated IR adipocytes decreased glucose uptake, without altering glycolysis or mitochondrial function. Interestingly, p-AMPK levels were increased rather than decreased in myotubes exposed to the CM of PCB126-treated IR adipocytes.ConclusionTaken together, these data suggest that increased adipokine secretion from IR adipocytes exposed to PCB126 may explain impaired glucose uptake in myotubes.

The Roles of p38 MAPK and ERK1/2 in Coplanar Polychlorinated Biphenyls-Induced Apoptosis of Human Extravillous Cytotrophoblast-Derived Transformed Cells

Background/Aims: The purpose of this study was to investigate the relationships among exposure to coplanar polychlorinated biphenyls (Co-PCBs), the expression of gC1qR and the underlying intracellular apoptotic signaling pathways of human extravillous cytotrophoblast (EVCT)-derived transformed cells (HTR-8/SVneo and HPT-8). Methods: Apoptosis in HTR-8/SVneo and HPT-8 cells was assessed using flow cytometric analysis. gClqR expression was examined in the HTR-8/SVneo and HPT-8 cells using real-time qPCR and western blot analyses. The phosphorylations of p38 mitogen-activated protein kinase (p38 MAPK) (Thr180/Tyr182) and extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Thr204) were detected using western blot analyses. Results: The HTR-8/SVneo and HPT-8 cells treated with Co-PCBs exhibited significantly increased gClqR expression, p38 MAPK/ERK activation and an up-regulation of cellular apoptosis. These effects were abrogated by the application of gC1qR small interfering RNA (siRNA). Furthermore, apoptosis in HTR-8/SVneo and HPT-8 cells was observed upon treatment with Co-PCBs, and these effects were reversed by the p38 MAPK pathway inhibitor SB203580 or the ERK1/2 pathway inhibitor PD098059. Conclusion: These data support a mechanism wherein gC1qR plays a crucial p38 MAPK/ERK signaling pathway-dependent role in Co-PCBs-induced apoptosis of human EVCT-derived transformed cells.

A direct method for the decontamination of a fly ash amended wet soil, artificially polluted with dioxins

We report hereby the first method of direct treatment of a wet soil containing toxic polychloroderivatives. Using a system with metallic Ca and 5% Rh fixed on charcoal in methanol, soil samples artificially polluted with fly ash containing polychloro-dibenzodioxins (PCDDs), polychloro-dibenzofurans (PCDFs) and coplanar polychlorinated biphenyls (co-PCBs), and having 69.2% to 84.6% moisture content, were successfully treated and decontaminated. This treatment afforded excellent hydrodechlorination yields for the 29 most toxic congeners of PCDDs, PCDFs and PCBs (98.3% degradation yield based on toxic equivalent quotient — or TEQ) after a 24 h treatment, at room temperature.