{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T19:40:28Z","timestamp":1791747628783,"version":"4.3.4"},"reference-count":59,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,2,23]],"date-time":"2015-02-23T00:00:00Z","timestamp":1424649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,4,15]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Although doxorubicin is a highly effective anti\u2010tumour agent, the administration of this drug is associated with significant side effects, including contractile dysfunction and myopathy of both cardiac and skeletal muscles. The mechanism(s) responsible for doxorubicin\u2010induced contractile dysfunction and myopathy in cardiac and skeletal muscles remains unclear.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In the present study, we report that increased mitochondrial oxidant production and calpain activation are major contributors to the development of doxorubicin\u2010induced myopathy. Moreover, treatment with a mitochondrial\u2010targeted peptide protects against doxorubicin\u2010induced mitochondrial dysfunction and myopathy in both heart and skeletal muscles.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These experiments provide insight into the mechanisms responsible for DOX\u2010induced contractile dysfunction and myopathy in cardiac and skeletal muscles. Importantly, our results may provide the basis for developing therapeutic approaches to prevent doxorubicin\u2010induced cardiac and skeletal muscle myopathy.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Although doxorubicin (DOX) is a highly effective anti\u2010tumour agent used to treat a variety of cancers, DOX administration is associated with significant side effects, including myopathy of both cardiac and skeletal muscles. The mechanisms responsible for DOX\u2010mediated myopathy remain a topic of debate. We tested the hypothesis that both increased mitochondrial reactive oxygen species (ROS) emission and activation of the cysteine protease calpain are required for DOX\u2010induced myopathy in rat cardiac and skeletal muscle. Cause and effect was determined by administering a novel mitochondrial\u2010targeted anti\u2010oxidant to prevent DOX\u2010induced increases in mitochondrial ROS emission, whereas a highly\u2010selective pharmacological inhibitor was exploited to inhibit calpain activity. Our findings reveal that mitochondria are a major site of DOX\u2010mediated ROS production in both cardiac and skeletal muscle fibres and the prevention of DOX\u2010induced increases in mitochondrial ROS emission protects against fibre atrophy and contractile dysfunction in both cardiac and skeletal muscles. Furthermore, our results indicate that DOX\u2010induced increases in mitochondrial ROS emission are required to activate calpain in heart and skeletal muscles and, importantly, calpain activation is a major contributor to DOX\u2010induced myopathy. Taken together, these findings show that increased mitochondrial ROS production and calpain activation are significant contributors to the development of DOX\u2010induced myopathy in both cardiac and skeletal muscle fibres.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jphysiol.2014.286518","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T08:11:01Z","timestamp":1422000661000},"page":"2017-2036","source":"Crossref","is-referenced-by-count":139,"title":["Increased mitochondrial emission of reactive oxygen species and calpain activation are required for doxorubicin\u2010induced cardiac and skeletal muscle myopathy"],"prefix":"10.1113","volume":"593","author":[{"given":"Kisuk","family":"Min","sequence":"first","affiliation":[{"name":"Department of Applied Physiology &amp; Kinesiology University of Florida  Gainesville FL 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