An Examination of the Proteasomal Rate of Degradation of Nuclear p65 in MDX Mice
Casey D. Stefanski*, Melanie Carr, Elizabeth Cottey , Amy Adams , and Corinna Warnars
Dr. C. George Carlson (AT Still University) and Dr. George Schulte, Faculty Mentors
Muscle from patients with Duchenne muscular dystrophy and from the mdx mouse, exhibit enhanced nuclear activation of NF-κB, which produces a deleterious effect on muscle structure and function. Recent evidence suggests that increase in the expression of the NF-κB component, p65, contributes to elevated nuclear activation in dystrophic muscle. To determine whether elevated p65 expression in dystrophic muscle is associated with reductions in the proteasomal degradation of nuclear p65, freshly isolated mdx and nondystrophic costal diaphragms were treated with the proteasome inhibitor MG132. Western blots of whole cell p65 expression indicate that MG132 treatment produced larger increases in whole cell p65 in nondystrophic muscle than in age matched mdx preparations. These preliminary results, which suggest that reductions in the rate of p65 degradation contribute to the enhanced nuclear NF-κB activation characteristic of dystrophic muscle, may provide a new avenue for treating Duchenne and related muscle diseases.
Keywords: Muscular Dystrophy, Mdx Mouse, MG132, NF-kB, Proteasome
Presentation Type: Poster
Location: Georgian Room - SUB