Why the study?
The mechanisms by which amelioration of mitochondrial ROS emission preserves cardiorespiratory muscle function following doxorubicin treatment remain unknown.
Does the mitochondria-targeted peptide SS-31 prevent doxorubicin-induced pathological proteolytic signaling in cardiac and skeletal muscle?
Population
Doxorubicin-treated animals
Comparison
SS-31 administration vs doxorubicin treatment alone
Design
Animal experimental study
Key result
Administration of SS-31 to DOX-treated animals prevented DOX-induced proteolytic signaling through ALS and UPP in the heart, while in the diaphragm ALS was inhibited but UPP was unaffected.
Authors
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May support mitochondrial ROS targeting to limit DOX myotoxicity; leaves open clinical translation.
Does the mitochondria-targeted peptide SS-31 prevent doxorubicin-induced pathological proteolytic signaling in cardiac and skeletal muscle?
Doxorubicin-induced mitochondrial ROS production plays distinct, muscle-specific roles in regulating proteolytic signaling in the heart versus the diaphragm, which can be differentially modulated by the mitochondria-targeted peptide SS-31.
Montalvo et al. (2019) studied Doxorubicin-induced cardiorespiratory muscle toxicity. SS-31 vs. Doxorubicin alone was evaluated on Proteolytic signaling by the autophagy/lysosomal system (ALS), ubiquitin-proteasome pathway (UPP), and unfolded protein response (UPR). Administration of SS-31 to DOX-treated animals prevented DOX-induced proteolytic signaling through ALS and UPP in the heart, while in the diaphragm ALS was inhibited but UPP was unaffected.