Shannon M. Bailey, PhD
Dept. of Environmental Health Sciences
School of Public Health
Office Address: RPHB 623
Websites: School of Medicine Faculty Profile
University of Oklahoma
BS, Zoology, 1989
University of Oklahoma Health Science Center
PhD, Pharmacology, 1996
Wake Forest University School of Medicine
Postdoctoral Research Fellow, Biochemistry, 1996-9
The long-term goal of my research is to determine the effects of chronic ethanol consumption on the system in the liver that plays a major role in hepatic energy metabolism, namely the mitochondrion. Specifically, my research focuses on the role of reactive inflammatory mediators in the development of ethanol-induced mitochondrial dysfunction. Studies related to this goal will establish the central role of the mitochondrion in the pathogenesis of alcoholic liver disease. The working hypothesis of these investigations is that chronic ethanolelicited alterations in mitochondrial structure and function result in increased production of reactive inflammatory mediators in liver of chronic alcohol abusers. Consequences of these ethanol-induced reactive species include the oxidative modification and inactivation of critical mitochondrial proteins, which results in mitochondrial dysfunction and cell death. Thus, our investigations focus on how chronic ethanol-induced increases in reactive species influence (1) mitochondria function and hepatic energy conservation and (2) the activity of several crucial antioxidant defense mechanisms present in liver mitochondria.
To address these research goals a rodent model of chronic alcohol consumption is used. Confocal microscopy is used to visually demonstrate that chronic ethanol-related increases in reactive species are primarily localized to the mitochondrion in isolated hepatocytes. Future studies will employ adenovirus-mediated gene transfer to selectively increase the levels of the antioxidant catalase in the cytosolic or mitochondrial compartments of hepatocytes isolated from control- and ethanol-fed rats. The ability of mitochondrial catalase overexpression to protect against chronic ethanol-elicited losses in ATP and cell viability will be determined in hepatocytes from ethanol-fed rats.
Proteomic analyses are underway to determine whether several mitochondrial antioxidants including glutathione peroxidase-1, thioredoxin reductase, and peroxiredoxin are susceptible to posttranslational oxidative modification and inactivation as a consequence of ethanol-induced reactive species. Ethanol-related oxidative modifications to proteins of the mitochondrial oxidative phosphorylation system are being investigated using the novel two-dimensional Blue Native-PAGE technique (see Figures for examples of these two techniques).
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