Date of Award

1-1-1998

Embargo Period

4-14-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Molecular and Cellular Biology and Pathobiology

College

College of Graduate Studies

First Advisor

Karl J. Karnaky, Jr.

Second Advisor

John E. Baatz

Third Advisor

Donald H. Miller

Fourth Advisor

Geoffrey I. Scott

Abstract

The killifish or mummichog, Fundulus heteroclitus, is an excellent indicator of environmental quality and ecosystems health. It is the most dominant endemic fish species found in the headwater of small estuarine tidal creeks in the southeastern U.S. and one of the most frequently studied animals for toxicological analysis. In the environment, these organisms are exposed to xenobiotic hydrophobic molecules from anthropogenic ( e.g., pesticides and combustion products) and natural ( e.g., decaying plants) sources. Development of physiological adaptations to both natural and anthropogenic stress is important to fish such as the mummichog which must deal with the rigors of an estuarine ecosystem. The transporter protein, P-glycoprotein (Pgp ), also called the multidrug resistance transporter protein, has been found in mammals and lower animals, including fish. I have shown that a Pgp-related protein is expressed in the liver of F heteroclitus employing the monoclonal antibody to mammalian form of P-glycoprotein, C219, using SDS PAGE and Western blot techniques. The goal of this investigation was to 2 characterize the putative xenobiotic transporter in the liver of F heteroclitus. This putative xenobiotic transporter has a molecular weight of 170 kDa and is glycosylated. In addition, this protein demonstrates the immunocytochemical localization and functionality that are normally associated with the mammalian MDR-1 protein. Moreover, competitive binding assays between C219, the liver of F heteroclitus, and a synthesized peptide containing the C219 epitope of human MDR-1, suggests that they contain a common epitope sequence. Therefore, it is hypothesized that this putative transporter protein is homologous to the multidrug resistance transporter protein (MDR 1) and plays an important role in how mummichogs adapt to consistent exposure to biogenic and anthropogenic contaminants.

Rights

Copyright is held by the author. All rights reserved.

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