EVALUATING POLOXAMERS AS AGENTS FOR ACCELERATION OF SKELETAL MUSCLE MEMBRANE REPAIR

Sarcolemmal membrane fragility is a major pathologic mechanism in various muscular dystrophies. Muscle fibers with more fragile membranes are more likely to be damaged and are more prone to necrosis. One potential therapeutic approach targeting membrane fragility is to increase membrane repair by ex...

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Bibliographic Details
Published inThe Ohio journal of science Vol. 118; no. 1; p. A51
Main Authors Rose, Aubrey L, Weisleder, Noah, Bodnar, Thomas A, Bhattacharya, Sayak, McElhanon, Kevin, Paleo, Brian J, Beck, Eric X
Format Journal Article
LanguageEnglish
Published Columbus Ohio Academy of Science 01.04.2018
Subjects
Attention Deficit Hyperactivity Disorder
Beads
Dyes
Exposure
Fibers
Fluorescence
Fluorescent dyes
Fluorescent indicators
Fragility
Glass beads
Hydrophobicity
Impact damage
L-Lactate dehydrogenase
Lactate dehydrogenase
Lactic acid
Laser damage
Lipid bilayers
Lipids
Lipophilic
Membranes
Muscles
Necrosis
Poloxamers
Polyoxyethylene
Repair
Skeletal muscle
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Summary:Sarcolemmal membrane fragility is a major pathologic mechanism in various muscular dystrophies. Muscle fibers with more fragile membranes are more likely to be damaged and are more prone to necrosis. One potential therapeutic approach targeting membrane fragility is to increase membrane repair by exposing muscle fibers to poloxamer 188 (P188), a polymer that is able to bind to exposed lipid bilayer to reseal membrane injuries. P188 is one of many poloxamers, all of which contain a hydrophobic region of polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene of varying length in different poloxamers. Although P188 has shown promise in increasing membrane repair, few other poloxamers have been tested for their effects on membrane repair. It was hypothesized that other poloxamers in the P188 family such as F38, P84, and P407 will reseal membranes as effectively, or more effectively, than P188. To investigate this hypothesis, a novel rotation damage assay was used, where cells are exposed to poloxamers and damaged through impact with small glass beads (106 pm diameter), and the lactate dehydrogenase (LDH) released from the cell into the supernatant is measured. Initial observations show that exposing cells to multiple poloxamers leads to a significant decrease in LDH levels when compared to vehicle controls, indicating improved membrane repair. A laser injury assay was used to confirm these results in muscle fibers that were damaged with a multiphoton laser to allow entry of a lipophilic dye. Entry of this fluorescent dye was measured over time to determine the membrane repair capacity.
ISSN:0030-0950
2471-9390