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The effects of doxorubicin on the mitochondrial dynamics and mitophagy machinery in varying types of skeletal muscles (1164.1)
Author(s) -
DirksNaylor Amie,
Yang Sendra,
Kouzi Samir
Publication year - 2014
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.28.1_supplement.1164.1
Subject(s) - mitophagy , fis1 , pink1 , skeletal muscle , mfn2 , parkin , oxidative stress , mitochondrion , apoptosis , chemistry , endocrinology , microbiology and biotechnology , medicine , autophagy , pharmacology , biology , mitochondrial fusion , biochemistry , parkinson's disease , mitochondrial dna , disease , gene
Doxorubicin (DOX) is an effective chemotherapeutic agent, known to cause cardiotoxicity via induction of oxidative stress and apoptosis. Despite toxic effects of DOX, few studies have investigated its effects in skeletal muscles. Multiple studies have examined DOX induced oxidative stress and mitochondrial dysfunction. However, no studies have investigated the effects of Dox on mitochondrial morphology and mitophagy. Thus, the first aim of the study was to determine the effects of DOX on the protein expression of primary regulators of mitochondrial morphology and mitophagy in skeletal muscle. The second aim was to investigate expression differences between three types of skeletal muscles varying in fiber type composition: diaphragm (DIA), extensor digitorum longus (EDL), and soleus (SOL). Male F344 rats were injected IP with 20 mg/kg of DOX or saline. Animals were fasted with no food or water until sacrifice 24 hours later. DOX treatment increased the protein content of DRP1, MFN2, and LC3‐I with no effect on FIS1, OPA1, MFN1, Parkin, PINK1, or p62. These effects were only observed in the DIA. Differences in expression levels between muscle types were present in FIS1, Parkin, LC3‐I, LC3‐II, and P62. In conclusion, DIA is more sensitive to the effects of DOX when compared to the EDL and SOL. Furthermore, the expression of regulators of mitochondria morphology and mitophagy varies among skeletal muscle types.