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Effect of Doxorubicin Treatment on Myogenic Regulatory Factor Protein Expression in Skeletal Muscle
Author(s) -
Quinn Colin,
Bredahl Eric,
Hayward Reid,
Hydock David
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.826.9
Subject(s) - myod , myf5 , myogenin , myogenic regulatory factors , skeletal muscle , myod protein , myocyte , transcription factor , endocrinology , medicine , chemistry , biology , biochemistry , myogenesis , gene
Doxorubicin (DOX) is an antineoplastic antibiotic used in a wide variety of cancer treatments. DOX treatment, however, has been linked to sarcomeric disruption and skeletal muscle weakness. Previous in vitro research has demonstrated that myocytes exposed to high levels of DOX had decreased myogenic regulatory factor (MRF) gene expression. The purpose of this study was to examine in vivo effects of DOX on MRF protein expression in skeletal muscles. Male Sprague Dawley rats were randomly assigned to receive DOX or saline, as a control. Five days after injections, the soleus and extensor digitorum longus (EDL) were excised and flash frozen until later analysis. Western blot was used to quantify MyoD, Myf5, Mrf4, and myogenin (MyoG) in muscles. Exposure to DOX significantly decreased expression of Myf5 and MyoD (muscle determination transcription factors), while elevating Mrf4 and MyoG (muscle differentiation transcription factors) in the soleus. In the EDL, however, only Mrf4 protein expression was significantly decreased. A reduction MRF expression committing cells to myogenic determination may be partially responsible for skeletal muscle sarcomere disruption and weakness following DOX administration.