Daniel Lark
Wasserman Lab
Last active: 9/26/2018

Targeted overexpression of mitochondrial catalase protects against cancer chemotherapy-induced skeletal muscle dysfunction.

Gilliam LA, Lark DS, Reese LR, Torres MJ, Ryan TE, Lin CT, Cathey BL, Neufer PD
Am J Physiol Endocrinol Metab. 2016 311 (2): E293-301

PMID: 27329802 · PMCID: PMC5005971 · DOI:10.1152/ajpendo.00540.2015

The loss of strength in combination with constant fatigue is a burden on cancer patients undergoing chemotherapy. Doxorubicin, a standard chemotherapy drug used in the clinic, causes skeletal muscle dysfunction and increases mitochondrial H2O2 We hypothesized that the combined effect of cancer and chemotherapy in an immunocompetent breast cancer mouse model (E0771) would compromise skeletal muscle mitochondrial respiratory function, leading to an increase in H2O2-emitting potential and impaired muscle function. Here, we demonstrate that cancer chemotherapy decreases mitochondrial respiratory capacity supported with complex I (pyruvate/glutamate/malate) and complex II (succinate) substrates. Mitochondrial H2O2-emitting potential was altered in skeletal muscle, and global protein oxidation was elevated with cancer chemotherapy. Muscle contractile function was impaired following exposure to cancer chemotherapy. Genetically engineering the overexpression of catalase in mitochondria of muscle attenuated mitochondrial H2O2 emission and protein oxidation, preserving mitochondrial and whole muscle function despite cancer chemotherapy. These findings suggest mitochondrial oxidants as a mediator of cancer chemotherapy-induced skeletal muscle dysfunction.

Copyright © 2016 the American Physiological Society.

MeSH Terms (17)

Animals Antineoplastic Agents Breast Neoplasms Catalase Disease Models, Animal Doxorubicin Electron Transport Complex I Electron Transport Complex II Female Hydrogen Peroxide Mice Mice, Transgenic Mitochondria, Muscle Muscle, Skeletal Muscle Contraction Oxidation-Reduction Proteins

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