Version 1
: Received: 14 March 2022 / Approved: 16 March 2022 / Online: 16 March 2022 (08:22:57 CET)
How to cite:
Travis, S. K.; Skinner, S. K.; Thome, T.; Fitzgerald, L. F.; Cohen, M. S.; Wolan, D. W.; Toth, M. J.; Ryan, T. E.; Hepple, R. T. Doxorubicin-Induced Skeletal Muscle Atrophy is Mediated by Mitochondrial Permeability Transition. Preprints2022, 2022030225. https://doi.org/10.20944/preprints202203.0225.v1
Travis, S. K.; Skinner, S. K.; Thome, T.; Fitzgerald, L. F.; Cohen, M. S.; Wolan, D. W.; Toth, M. J.; Ryan, T. E.; Hepple, R. T. Doxorubicin-Induced Skeletal Muscle Atrophy is Mediated by Mitochondrial Permeability Transition. Preprints 2022, 2022030225. https://doi.org/10.20944/preprints202203.0225.v1
Travis, S. K.; Skinner, S. K.; Thome, T.; Fitzgerald, L. F.; Cohen, M. S.; Wolan, D. W.; Toth, M. J.; Ryan, T. E.; Hepple, R. T. Doxorubicin-Induced Skeletal Muscle Atrophy is Mediated by Mitochondrial Permeability Transition. Preprints2022, 2022030225. https://doi.org/10.20944/preprints202203.0225.v1
APA Style
Travis, S. K., Skinner, S. K., Thome, T., Fitzgerald, L. F., Cohen, M. S., Wolan, D. W., Toth, M. J., Ryan, T. E., & Hepple, R. T. (2022). Doxorubicin-Induced Skeletal Muscle Atrophy is Mediated by Mitochondrial Permeability Transition. Preprints. https://doi.org/10.20944/preprints202203.0225.v1
Chicago/Turabian Style
Travis, S. K., Terence E. Ryan and Russell T. Hepple. 2022 "Doxorubicin-Induced Skeletal Muscle Atrophy is Mediated by Mitochondrial Permeability Transition" Preprints. https://doi.org/10.20944/preprints202203.0225.v1
Abstract
Doxorubicin (Dox) is a commonly used chemotherapeutic that can adversely affect skeletal muscle, including causing muscle atrophy. Dox is known to induce an event known as mitochondrial permeability transition (MPT) in cardiac muscle and this plays an important role in Dox-mediated cardiac toxicity. Further to this, recent evidence identifies MPT as a mechanism of atrophy in skeletal muscle, suggesting that MPT may underlie some of the Dox-related toxicity in skeletal muscle. To test this hypothesis, we used cultured human primary myotubes, C2C12 myotubes, and single adult mouse flexor digitorum brevis (FDB) muscle fibers in experiments involving Dox treatment with or without inhibitors of MPT. Dox treatment of myotubes caused myonuclear translocation of the mitochondrial protein apoptosis inducing factor (AIF) and increased mitochondrial reactive oxygen species (mROS), consistent with the known consequences of MPT. Furthermore, Dox caused atrophy in C2C12 myotubes grown on patterned plates, human primary myotubes, and single muscle fibers from adult mice. Notably, Dox-induced atrophy could be prevented by a wide variety of agents that inhibit MPT, as well as by inhibiting mROS or Caspase 3. In conclusion, our results indicate that MPT plays an important role in driving Dox-mediated skeletal muscle atrophy.
Keywords
chemotherapy; muscle atrophy; Doxorubicin; mitochondria; reactive oxygen species
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.