There is increasing experimental evidence to support the concept of free radical damage to cellular constituents. In general, an increase in free radical generation would lead to alterations of biochemical and biophysical properties of cells. The process of free radical generation may also be important in the pathological manifestations of aging and alcoholism. The overall objective of this project is to investigate the involvement of free radicals in brain membrane deterioration, and to examine whether alcohol- enhanced free radical formation will affect the aging process. Specifically, experiments will be designed to (1) test the hypothesis that free radicals play and important role in the aging process, and that ethanol accelerates aging process through potentiation or enhancement of the lipid peroxidation process; (2) evaluate specific membrane-dependent processes with respect to aging and chronic ethanol administration; (3) study the body protective system in brain against the toxic effects of free radical attack and (4) evaluate the importance of dietary antioxidants, such as vitamins E and C, in providing protection against the peroxidative damage resulted from alcohol ingestion. For experiments described in this project, we will continue to use C57BL/6NNIA mice as the animal model. The spin trapping technique will be employed to detect free radical formation in both in vitro and in vivo systems. In addition, the activity of enzymes involved in metabolism of the peroxidation process in brain, such as supreoxide dismutase, catalase, and glutathione peroxidase will also be investigated. Since many neuronal membrane processes are known to depend on the microenvironment of membrane lipids for proper functioning, we will specifically examine the effects of age and alcohol and (Na+, K+)-ATPase activity, enzyme its kinetics, phosphorylated intermediates and ouabain binding properties in mouse synaptic plasma membranes. In addition, other membrane-bound enzymes which are important in modulating membrane lipids will be examined and tested for their sensitivity to the radical formation. It is anticipated that through this systematic investigation, new information may be obtained regarding the mechanism of membrane deterioration due to age and/or alcohol intake, and the effectiveness of dietary supplement of vitamin E and vitamin C on alleviating some of the changes due to aging and/or alcohol abuse.
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