Gilliam 2016 Am J Physiol Endocrinol Metab
|Gilliam LA, Lark DS, Reese LR, Torres MJ, Ryan TE, Lin CT, Cathey BL, Neufer PD (2016) Targeted overexpression of mitochondrial catalase protects against cancer chemotherapy-induced skeletal muscle dysfunction. Am J Physiol Endocrinol Metab 311:E293-301.|
Gilliam LA, Lark DS, Reese LR, Torres MJ, Ryan TE, Lin CT, Cathey BL, Neufer PD (2016) Am J Physiol Endocrinol Metab
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.
Copyright © 2016 the American Physiological Society. • Keywords: Cancer, Chemotherapy, Mitochondria, Reactive oxygen species, Skeletal muscle, Buffer z, Blebbistatin, Amplex Red
• O2k-Network Lab: US TN Nashville Wasserman DH, US NC Greenville Neufer PD
Labels: MiParea: Respiration, Genetic knockout;overexpression, Pharmacology;toxicology Pathology: Cancer Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS Pathway: F, N, NS, Other combinations HRR: Oxygraph-2k