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(P713) PGP as a potential biomarker for meiofaunal exposure to contaminants.
Griffitt, Joe*,1, Chandler, Tom1, Coull, Bruce2, Staton, Joe3, 1 NJA School of Public Health, University of South Carolina, Columbia, SC, USA2 School of the Environment, University of South Carolina, Columbia, SC, USA3 Belle W. Baruch Institute, University of South Carolina, Columbia, SC, USA
ABSTRACT- P-glycoproteins are members of the poorly understood Multi-Drug Resistance class of proteins. They act as ATP-driven pumps that can actively transport a wide variety of structurally unrelated, hydrophobic cytotoxins outside the cell. They were first observed in human cancer cells, where over-expression of the protein was correlated with decreased intracellular concentration and increased efflux rates of drugs being used to treat the cancer. Multiple PGP genes have since been found in all animal taxa examined to date, including free-living and parasitic nematodes, where they contribute resistance to the potent anthelmintic agents ivermectin and moxidectin, as well as heavy metals. Resistance seems to have a short and long term response, as both upregulation of the protein and selection for a particular allele occur in response to exposure of parasitic nematodes to nematicides. This resistance can be mediated by verapamil, which is thought to inhibit proper functioning of the PGP protein. The genetic sequence coding for a PGP protein has been published for a number of taxa, and it shows a high degree of conservation at the amino acid level. Thus we have begun working to develop the PGP-A gene as a biomarker to assess contaminant exposure in free-living estuarine nematodes. Using previously published PGP sequences from the nematodes Caenorhabditis elegans, Haemonchus contortus, and Onchocerca volvulus we have designed a series of degenerate primers to amplify a section of PGP from cultures of the estuarine nematode, Cylindrotheristus miamiensis. Using extracted RNA, we have been able to amplify a region of the PGP gene from cDNA. This information has been used to design species specific primers to allow amplification of this region from individual nematodes. This work will allow us to look both at allelic selection in response to toxicant exposure history, as well as upregulation of the PGP-A gene product.
Key words: P-glycoproteins, nematode, biomarker
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