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Although molecular oxygen
is indispensable for aerobic life forms, it is
also a universal toxicant that can cause oxidative
damage in a variety of biological molecules, leading
to a phenomenon known as oxidative stress. Oxidative
stress is an important causal or contributing
factor in a variety of pathological conditions
in humans, including atherosclerosis, certain
forms of cancer, and several neurodegenerative
diseases, such as Parkinsonism and Alzheimer's
disease. My group's research interests focus on
the general theme of mechanisms of biological
oxidations. We are particularly interested in
defining how byproducts from one type of oxidative
stress, known as lipid peroxidation, result in
chemical modification of proteins and other biomolecules.
Lipid peroxidation.
Projects in this area range from basic mechanistic
studies of oxidative damage in simple model systems
to collaborative clinical studies in which we
are assessing antioxidant effects on the rate
of progression of cognitive dysfunction in elderly
subjects.
Synthetic antioxidants.
The antioxidant resveratrol has attracted interest
since it is one of the major phenolic antioxidants
in red wine. We are synthesizing a series of structural
analogs of resveratrol and assessing their antioxidant
activities in efforts to define structure/activity
relationships that afford enhanced protection
of lipid bilayers and human serum lipoproteins
against oxidative damage.
Biomarkers of oxidative
damage. In this
project, we are isolating and characterizing fluorescent
components from human serum that we have previously
shown increase with age and which have been proposed
as indicators of in vivo lipid oxidation. Characterization
of these species is an important milestone for
their future clinical use as surrogate biomarkers
for oxidative stress in humans.
Membrane control of
cytochrome P450 activity.
An ever-increasing number of membrane proteins
and enzymes have been shown to be sensitive to
modulation of the lipid environment of the membrane
in which they reside. To better understand this
mode of enzyme regulation, we are studying the
effects of lipid compositional changes on the
activity and regioselectivity of a purified mammalian
cytochrome P450 reconstituted into synthetic lipid
vesicles.
Recent publications:
1. D.W. Seybert and C.M. Milnar.
Antioxidant activity of resveratrol analogs in
phospholipid oxidation. Free Radic. Biol. Med.
25, S37 (1998).
2. Owens, J.W., M.B. Perry,
and D.W. Seybert. Reactions of nitric oxide with
cobaltous tetraphenylporphyrin and phthalocyanines.
Inorg. Chim. Acta 277(1), 1-7 (1998).
3. Hanlon, M.C. and D. W. Seybert.
The pH dependence of lipid peroxidation using
water-soluble azo initiators. Free Radical Biol.
Med. 23, 712-719 (1997)
4. Warburton, R.J. and D. W.
Seybert. Structural and functional characterization
of bovine adrenodoxin reductase by limited proteolysis.
Biochim. Biophys. Acta 1246, 39-46 (1995).
Office Phone:(412) 396-6465
Email:seybert@duq.edu
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