Mitochondrial OXPHOS functions in R1H rhabdomyosarcoma and skeletal muscles of the rat.
The aim of the study was to determinate mitochondrial oxidative phosphorylation (OXPHOS) functions in rat rhabdomyosarcoma R1H (R1H) and rat skeletal muscles. For that purpose skinned fiber technique and multiple substrate inhibitor titration were adapted to tumor samples. In our animal tumor model (R1H) functional abnormalities of OXPHOS were found compared to skeletal muscles. In R1H the state 3 respiration of pyruvate + malate was decreased: 0.56 +/- 0.28 nmol O(2)/mg/min versus 2.32 +/- 1.19 nmol O(2)/mg/min, P < 0.001, whereas the state 3 respiration of succinate + rotenone was increased: 36 +/- 14% versus 19 +/- 11%, P < 0.001. In R1H the rotenone-insensitive respiration reached higher levels than the antimycin A-insensitive respiration, whereas in normal muscles the converse was observed. Additionally, the obvious difference between the CAT- and the antimycin A-independent respiration indicates an increased part of leak respiration in R1H. By now, the high feasibility of these techniques is appreciated for the investigation of muscles and prospectively for tumors, too.
Kuhnt
Thomas
T
Department of Radiotherapy, Martin-Luther-University, Halle-Wittenberg, Halle, Saale, Germany. thomas.kuhnt@medizin.uni-halle.de
Pelz
Tanja
T
Qu
Xiaoying
X
Hänsgen
Gabriele
G
Dunst
Jürgen
J
Gellerich
Frank Norbert
FN
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D045744:Cell Line, Tumor; D004579:Electron Transport / Q000187:drug effects; D005260:Female; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012208:Rhabdomyosarcoma / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology; D013386:Succinates / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
D013386:Succinates; D014475:Uncoupling Agents; D012402:Rotenone; D000968:Antimycin A; D019289:Pyruvic Acid