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Modulating Membrane Repair Facilitates Therapeutic Cell Membrane Resealing in Striated Muscle
Author(s) -
Gushchina Liubov,
Bhattacharya Sayak,
Blazek Alisa,
Manring Heather,
Beck Eric,
Alloush Jenna,
Weisleder Noah
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.801.1
Subject(s) - dysferlin , skeletal muscle , muscular dystrophy , myocyte , medicine , limb girdle muscular dystrophy , myopathy , endocrinology , chemistry , biochemistry , mutation , gene
Muscular dystrophy is a broad group of inherited muscle diseases characterized by wasting and weakness of skeletal muscle. Mutations in dysferlin are linked to Miyoshi myopathy and limb‐girdle muscular dystrophy type 2B (LGMD2B), two clinically distinct muscle diseases. The mechanism that leads to muscle degeneration has not been fully resolved. Mitsugumin 53 (MG53), also known as muscle‐specific tripartite motif 72, is a recently identified protein involved in membrane repair in skeletal muscle. The protective effect of rhMG53 protein against tissue damage in skeletal and heart muscles has been shown in rodent models. To study the physiological function of rhMG53 in the dysferlin‐deficient mouse model, we induced muscle membrane damage in 12‐week‐old mice during a single round of eccentric exercise. For the rhMG53‐treated group, rhMG53 was injected IP once, 1 hour before starting treadmill exercise (40 min, 18 m/min). A non‐treated control group was exercised using the same conditions. To confirm the protective effect of rhMG53 after treatment on sarcolemmal permeability and fiber necrosis, gluteus and soleus muscle sections of dysferlin‐deficient mice were stained with fluorescent‐labeled goat anti‐mouse IgG and the number of IgG‐negative/positive fibers was counted. Serum CK and LDH levels were measured. Our study showed that a one time intraperitoneal injection of rhMG53 prior to the treadmill exercise decreased the number of IgG‐positive fibers and serum CK and LDH levels. Thus, rhMG53 protein can be an effective therapeutic agent in preventing the development of muscular dystrophy in a patient with LGMD2B.