Modulation of muscle protein metabolism in disseminated intravascular coagulation.
Muscle protein degradation and intracellular protease activities were investigated in disseminated intravascular coagulation (DIC), which is frequently associated with severe catabolic states such as sepsis and multiple organ failure. DIC was introduced in rats by repeated intravenous thrombin injections. Saline was injected in control rats. In the 28 rats (14 with DIC and 14 controls), the bilateral soleus (SOL) muscles were incubated in an oxygenated medium without cycloheximide (CH) to determine the release of tyrosine (Tyr) into the incubated medium. From 24 rats (12 with DIC and 12 controls), the SOL and extensor digitorum longus (EDL) muscles were harvested to measure the activities of proteasome and of cathepsins L and B. The contralateral muscles were incubated in a medium with 0.5 mM CH to determine the release of Tyr and 3-methylhistidine (3-MH). The release of Tyr without CH (net proteolysis) from SOL muscles with DIC was greater than in controls (218 +/- 83.3 vs. 145 +/- 47.7 pmol/mg/h. However, the release of Tyr and 3-MH with CH (total proteolysis) and the activities of proteasome and cathepsins in DIC were nearly the same as those in controls. In both DIC and control rats, the total release of Tyr and proteasome activity were greater in SOL than in EDL muscles. These results suggest that reutilization of Tyr, reflecting protein synthesis, is suppressed in DIC and that the red slow muscle is more active in nonfibrillar proteolysis than the white fast muscle.
Tsujinaka
T
T
Department of Surgery II, Osaka University Medical School, Japan.
Homma
T
T
Ebisui
C
C
Fujita
J
J
Kido
Y
Y
Yano
M
M
Shibata
H
H
Tanaka
T
T
Mori
T
T
D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004211:Disseminated Intravascular Coagulation / Q000378:metabolism*; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D009097:Multienzyme Complexes; D009124:Muscle Proteins; D014443:Tyrosine; D002403:Cathepsins; D010447:Peptide Hydrolases; D013917:Thrombin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex