Hyperthermia stimulates energy-proteasome-dependent protein degradation in cultured myotubes.
Previous studies suggest that elevated temperature stimulates protein degradation in skeletal muscle, but the intracellular mechanisms are not fully understood. We tested the role of different proteolytic pathways in temperature-dependent degradation of long- and short-lived proteins in cultured L6 myotubes. When cells were cultured at different temperatures from 37 to 43 degrees C, the degradation of both classes of proteins increased, with a maximal effect noted at 41 degrees C. The effect of high temperature was more pronounced on long-lived than on short-lived protein degradation. By using blockers of individual proteolytic pathways, we found evidence that the increased degradation of both long-lived and short-lived proteins at high temperature was independent of lysosomal and calcium-mediated mechanisms but reflected energy-proteasome-dependent degradation. mRNA levels for enzymes and other components of different proteolytic pathways were not influenced by high temperature. The results suggest that hyperthermia stimulates the degradation of muscle proteins and that this effect of temperature is regulated by similar mechanisms for short- and long-lived proteins. Elevated temperature may contribute to the catabolic response in skeletal muscle typically seen in sepsis and severe infection.
Luo
G J
GJ
Department of Surgery, University of Cincinnati, and Shriners Hospital for Children, Cincinnati, Ohio 45267, USA.
Sun
X
X
Hasselgren
P O
PO
D000818:Animals; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D009097:Multienzyme Complexes / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D013696:Temperature
D009097:Multienzyme Complexes; D009124:Muscle Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex