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Gilliam 2013 Free Radic Biol Med
Coupling states OXPHOS  + , ET  +
Diseases Cancer  +
Has abstract The combined loss of muscle strength and c
The combined loss of muscle strength and constant fatigue are disabling symptoms for cancer patients undergoing chemotherapy. Doxorubicin, a standard chemotherapy drug used in the clinic, causes skeletal muscle dysfunction and premature fatigue along with an increase in reactive oxygen species (ROS). As mitochondria represent a primary source of oxidant generation in muscle, we hypothesized that doxorubicin could negatively affect mitochondria by inhibiting respiratory capacity, leading to an increase in H2O2-emitting potential. Here we demonstrate a biphasic response of skeletal muscle mitochondria to a single doxorubicin injection (20 mg/kg). Initially at 2 h doxorubicin inhibits both Complex I- and II-supported respiration and increases H2O2 emission, both of which are partially restored after 24 h. The relationship between oxygen consumption and membrane potential (Δ''Ψ''(mt)) is shifted to the right at 24 h, indicating elevated reducing pressure within the electron transfer-pathway (ET-pathway). Respiratory capacity is further decreased at a later time point (72 h) along with H2O2-emitting potential and an increased sensitivity to mitochondrial permeability transition pore (mtPTP) opening. These novel findings suggest a role for skeletal muscle mitochondria as a potential underlying cause of doxorubicin-induced muscle dysfunction.
of doxorubicin-induced muscle dysfunction.  +
Has info [ PMID: 24017970 Open Access]  +
Has publicationkeywords Chemotherapy  + , Metabolism  + , Mitochondria  + , PmFBs  + , ROS  + , Reactive oxygen species  + , Skeletal muscle  + , TPP  + , electron transport system  + , mPTP  + , mitochondrial permeability transition pore  + , permeabilized fiber bundles  + , reactive oxygen species  + , tetraphenylphosponium  + , ET-pathway  +
Has title Gilliam LA, Fisher-Wellman KH, Lin CT, Maples JM, Cathey BL, Neufer PD (2013) The anticancer agent doxorubicin disrupts mitochondrial energy metabolism and redox balance in skeletal muscle. Free Radic Biol Med 65:988-96.  +
Instrument and method Oxygraph-2k  + , TPP  +
Mammal and model Rat  +
MiP area Respiration  + , mt-Membrane  + , Pharmacology;toxicology  +
Pathways N  + , S  +
Preparation Permeabilized tissue  +
Stress Permeability transition  +
Tissue and cell Skeletal muscle  +
Was published by MiPNetLab US NC Greenville Neufer PD +
Was published in journal Free Radic Biol Med +
Was published in year 2013  +
Was written by Gilliam LA + , Fisher-Wellman KH + , Lin CT + , Maples JM + , Cathey BL + , Neufer PD +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
12:19:36, 13 November 2017  +
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