2012 Trainee Webinar Series
Session III: Featuring Lauren Tetz (University of Michigan – Northeastern University) and Fabian Grimm (University of Iowa)
August 1, 2012; 1:00 PM - 2:00 PM, Eastern Daylight Time
Lauren Tetz: Mono-2-Ethylhexyl Phthalate-Induced Oxidative Stress in Human Placental Cells
Exposure to di-2-ethylhexyl phthalate (DEHP), an environmental contaminant used as a plasticizer, increases risk of adverse pregnancy outcomes in humans. Moreover, monoethylhexyl phthalate (MEHP), the active metabolite of DEHP, increases oxidative stress responses in vitro, which is linked to the pathogenesis of preterm birth. The researchers investigated MEHP stimulated oxidative stress in human placental cells as a mechanism by which MEHP exposure may contribute to preterm birth. They treated human placental cells with MEHP and measured reactive oxygen species (ROS) generation. They found that MEHP increased ROS generation, oxidative DNA damage, and apoptosis, and modified redox-sensitive gene expression. Notably, MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the gene for COX-2, an enzyme important for prostaglandin synthesis and labor initiation. These findings warrant future epidemiological studies of oxidative stress as a mechanism by which MEHP may contribute to preterm birth and other adverse pregnancy outcomes.
Fabian Grimm: Sulfated Metabolites of Polychlorinated Biphenyls are High-Affinity Ligands for Human Transthyretin
Exposure to polychlorinated biphenyls (PCBs), environmentally persistent hazardous chemicals, is related to pathological abnormalities of the thyroid gland and decreased serum levels of thyroid hormones. Certain hydroxylated metabolites of PCBs (OHPCBs) are capable of displacing L-thyroxine from transthyretin (TTR). Some OHPCBs are excellent substrates for cytosolic sulfotransferases that catalyze the formation of sulfate conjugates, but little is known about the fate or toxicities of these sulfate esters. PCB sulfates structurally resemble thyroxine and may represent a second class of high affinity ligands for thyroxine binding sites on TTR. To test this, the sulfate esters of five mono‐hydroxylated PCB congeners and their respective OHPCBs were examined for their ability to bind to human TTR. All five PCB sulfates were able to bind to the high-affinity binding site with Kd values similar to those determined for their respective OHPCB precursors and for L-thyroxine. In addition, the binding interactions of PCB sulfates to TTR were found to be non-covalent and fully reversible. Molecular docking simulations were utilized to calculate the lowest energy binding conformations of these PCB sulfates within the thyroxine binding site of human TTR, thereby providing corroborating evidence for their binding potential. Moreover, the corresponding OHPCBs were found to be substrates for human and rat forms of sulfotransferase 1A1. These results on the binding of PCB‐sulfates to TTR suggest a potential relevance in PCB‐mediated thyroid disruption.
Session II: Featuring Dena Cologgi (Michigan State University) and Richard Meggo (University of Iowa)
July 5, 2012; 1:00 PM – 2:00 PM, Eastern Daylight Time
Dena Cologgi: Novel Mechanism of Uranium Reduction via Microbial Nanowires
The in situ stimulation of metal reduction by Geobacter bacteria shows promise for the reductive precipitation of uranium contaminants. However, the mechanism behind this reaction has remained elusive. As bacterial cells are nanostructured interfaces that employ defined components to catalyze chemical reactions, our team sought to investigate the mechanism of U reduction by Geobacter bacteria in vivo to develop biomimetic nanoplatforms for U removal. U reduction during in situ bioremediation is concomitant to the reduction of Geobacter's natural electron acceptor, Fe(III) oxides, a process that requires the production of conductive protein filaments termed pilus nanowires. Thus, we investigated a potential role for the nanowires in U reduction by testing the ability of pili-expressing and nonexpressing strains of the model organism Geobacter sulfurreducens to remove soluble hexavalent U (U(VI)) and reduce it to the less mobile tetravalent U (U(IV)).
Richard Meggo: Rhizosphere Biotransformation Products of Selected PCB Cogeners
Reductive dechlorination followed by aerobic bio-oxidation is necessary to achieve complete degradation of mixtures of higher and lower chlorinated PCBs. Plant rhizospheres are known to support large and diverse populations of microorganisms by providing an ample supply of electron donors. It is hypothesized that manipulation of soil moisture content in plant rhizosphere can produce fluctuations in redox potential which may be able facilitate both reductive dechlorination and aerobic bio-oxidation. Soil artificially contaminated with a mixture of hexa and tetra chlorinated PCB congeners is planted with switchgrass and subjected to sequential cycles of high and moisture content. The dissipation of the parent compounds in the mixture and the formation of transformation products is investigated and reported.
Session I: Featuring Bei Zhang (University of Kentucky) and Corin Hammond (University of Arizona)
February 21, 2012; 1:00 - 2:00pm, Eastern Daylight Time
Bei Zhang: Cerebrovascular Toxicity of PCBs Bound to Nanoparticles in the Experimental Stroke Model
Polychlorinated biphenyls (PCBs) are organochlorinated chemicals that are persistent in the environment due to their structural stability and high lipophilicity. Recent evidence suggests that exposure to PCBs may increase the incidence of stroke and worsen stroke outcomes. PCBs released from environmental sources are capable of binding onto nanoparticles present in the environment and being taken up by humans. However, the toxicity of PCBs assembled onto nanoparticles is unknown. In the current study, the research team hypothesizes that binding to nanoparticles can potentiate PCB-induced vascular toxicity and brain damage in an experimental stroke model through activation of toll-like receptor 4 (TLR4), stimulation of inflammatory responses, and alterations of tight junction protein expression in brain capillaries.
Corin Hammond: Biogeochemical Transformation of Metal(loid)s during Phytostabilization of Iron King Mine Tailings, Dewey-Humboldt, Arizona
The Iron King Mine-Humboldt Smelter Site, which was added to the National Priorities List in 2008, comprises a large mass of exposed un-vegetated mine tailings with high concentrations of arsenic and lead contained in relatively small particles. The tailings pose a health risk to adjacent communities from possible water- and air-borne exposure. A randomized-block field trial is currently underway to test “phytostabilization” of the tailings and associated contaminants via establishment of a vegetative cap. Since plant germination is hindered by an inhospitable geochemical environment (low organic matter, high acidity and toxic metal concentrations), composted organic matter and irrigation water are being added to promote plant growth. This research focuses on evaluation of the efficacy of phytostabilization as a bioremediation approach to the smelter site. To assess changes in contaminant lability in relation to molecular speciation over the course of tailings bio-colonization, the researchers are combining analytical wet chemistry (sequential extraction, cascade filtration) with synchrotron-based X-ray methods (XANES, EXAFS, XRD) as a function of time and specific treatment.