Project Summary for The MBRS Program, CSUN

Dr. Sandra L. Jewett
(818) 677-4503

Long term objectives:

To quantify the nonspecific peroxidase activity of the CuZn-superoxide dismutase in the SOD/H2O2 system.

Background:

The CuZn-superoxide dismutase in an important antioxidant enzyme which guards aerobic cell against increases in the toxic superoxide anion.  This enzyme provides the first line of defense against toxic reactions of molecular oxygen.
Reaction catalyzed: 2O2- + 2H+                     H2O2 + O2
                                   
superoxide anion            hydrogen peroxide

Importance:

the non-specific peroxide activity may be a contributing factor to cell damage in the following disease states or cellular processes:
-in
FALS (familial amyotropic lateral sclerosis, or Lou Gehrig's disease) where mutations have a gain-of-function.
-
Diabetes where autoxidation of SOD lead to peroxide formation.
-in
down's syndrome where increased amounts of dismutase leads to increased amounts of  H2O2 production.
-In
apoptosis, or programmed cell death, which is sensitive to levels of superoxide anion and other reactive oxygen species.
-in deleterious effects of dismutase in pharmaceutical preparations with other antioxidants whose autooxidation produces peroxides.

These fundamental studies will contribute to understanding not only the nonspecific peroxidase activity of the dismutase and how that might relate to the gain-of-function of mutant SOD in ALS where cell damage leads to neuronal death.  These studies will also contribute to the understanding how the enzyme itself may contribute to cell death in Down's syndrome, diabetes, and apoptosis.

Summary:

Experimental Methods:

Enzyme activity analyses                          Lowry protein analysis
Native and SDS gel electrophoresis        Metal analysis
Spectrophotometric analyses                Oxygraph analysis of H2O2
KMnO4 titration's of H2O2

Computer Analyses (PC Based):

Excel analyses, Word Perfect and or Microsoft Word

Report Writing:

Journal format

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