Skeletal muscle protease activities are unaltered in cirrhotic rats but altered in response to ethanol and acetaldehyde in vitro.
This study was carried out in an attempt to differentiate between the contribution of liver impairment and direct actions of alcohol in myopathy of alcoholic liver disease. Using an animal model of cirrhosis we have previously shown that protein synthetic potential in muscle was not significantly altered. We therefore investigated the possibility that muscle degradation is increased. Cirrhosis was induced by carbon tetrachloride gavage in male rats receiving phenobarbitone in their drinking water. Controls were given phenobarbitone alone. After 135 days the free, latent and total activities of the lysosomal enzymes cathepsin B and cathepsin D in gastrocnemius muscle were unaffected by the induction of experimental cirrhosis when expressed relative to tissue wet weight, protein or DNA. The non-lysosomal enzyme neutral protease was also measured in gastrocnemius muscle from control and cirrhotic rats. There was no difference between the two groups in the free, latent or total activities. Addition of ethanol and acetaldehyde to the assay mixtures in some cases significantly altered the relative activities of the proteases in latent and free compartments of the cirrhotic tissues. In control tissues a different pattern of response emerged. It is concluded that in cirrhosis, at least in the carbon tetrachloride-induced rat model, there is no change of the activity of cathepsin B and D and the neutral protease activity in gastrocnemius. Small but significant effects of ethanol and its metabolite acetaldehyde on latent and free muscle protease activity were demonstrated.
Cook
E B
EB
Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, UK.
Gove
C D
CD
Panos
M Z
MZ
Williams
R
R
Preedy
V R
VR
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology*; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D009124:Muscle Proteins; D000431:Ethanol; D010450:Endopeptidases; D002401:Cathepsin B; D002402:Cathepsin D; D000079:Acetaldehyde