Evaluating Poloxamers as Agents for Acceleration of Skeletal Muscle Membrane Repair
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Publisher:The Ohio State University
Series/Report no.:The Ohio State University. Department of Molecular Genetics Honors Theses; 2018
Sarcolemmal membrane fragility is a major contributor to the pathology of various muscular dystrophies, including Duchenne Muscular Dystrophy (DMD). DMD is a fatal X- linked genetic disorder resulting from a loss of the dystrophin protein. This causes muscle degeneration and weakness, in both skeletal and cardiac tissue. Muscle fibers with more fragile membranes experience a higher degree of damage and are more prone to necrotic cell death. Increasing the membrane repair capacity of these fibers can serve as a potential therapeutic by effectively restoring the barrier function of the damaged membrane and prevent muscle fiber death and muscle loss. One strategy to increase the membrane repair capacity is to expose the muscle fibers to Poloxamer 188 (P188), a polymer with affinity to exposed hydrophobic lipid chains that can reseal membrane wounds. P188 is part of a family of poloxamers, all of which contain a hydrophobic region of polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene. These regions vary in length between different poloxamers. Although P188 has shown promising results in membrane repair, other poloxamers in this family have not been tested for their membrane sealing capacity. It is hypothesized that other poloxamers in the P188 family such as F38, P84, and P407 will reseal membrane wounds as or more effectively than P188. To investigate this hypothesis, we used both a rotation damage assay and a laser injury assay to examine the repair efficiency of poloxamers on in vitro human embryonic kidney (HEK293) cells and ex vivo muscle fibers isolated from mdx mice. Studying the effect of these compounds on muscle fibers with compromised membrane integrity allowed for the evaluation of these poloxamers as potential therapeutic agents for muscular dystrophy. The conclusion of these assays indicates that there are poloxamers other than P188 that can improve the repair capacity in both HEK293 cells and dystrophic mdx muscle fibers.
Academic Major: Molecular Genetics
Mayers Summer Research Scholarship