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Am J Physiol Endocrinol Metab. 2016 Aug 1;311(2):E293-301. doi: 10.1152/ajpendo.00540.2015. Epub 2016 Jun 21.

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

Author information

1
East Carolina Diabetes and Obesity Institute, Department of Physiology, and.
2
East Carolina Diabetes and Obesity Institute, Department of Kinesiology, East Carolina University, Greenville, North Carolina.
3
East Carolina Diabetes and Obesity Institute, Department of Physiology, and Department of Kinesiology, East Carolina University, Greenville, North Carolina.

Abstract

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.

KEYWORDS:

cancer; chemotherapy; mitochondria; reactive oxygen species; skeletal muscle

PMID:
27329802
PMCID:
PMC5005971
DOI:
10.1152/ajpendo.00540.2015
[Indexed for MEDLINE]
Free PMC Article

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