Lysosomal and nonlysosomal protease activities of the brain in response to ethanol feeding.
The contribution of impaired degradative processes to the cellular changes occurring in the brain as a consequence of chronic ethanol exposure was assessed. Male Wistar rats were fed nutritionally adequate liquid diets containing ethanol as 35% of total dietary calories. Controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. The results showed that at the end of 3 weeks the activities of neutral protease (nonlysosomal) and cathepsin D (lysosomal) were unaltered. However, there were significant elevations in the activities of the lysosomal enzyme cathepsin B, regardless of whether the activities were expressed relative to wet weight ( p = 0.005), protein (p = 0.006), or DNA (p = 0.045). In addition, we showed that the activities of cathepsin B were not significantly affected by additions of carnosine or acetaldehyde, in vitro. However, neutral protease activities were increased by carnosine additions in vitro. We conclude that selective alterations in brain protease activities may be contributing factors in the genesis of alcoholic brain disorders.
Bonner
A B
AB
Addictive Behaviour Centre, Roehampton Institute London, West Hill, UK.
Swann
M E
ME
Marway
J S
JS
Heap
L C
LC
Preedy
V R
VR
D000079:Acetaldehyde / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002336:Carnosine / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004032:Diet; D010450:Endopeptidases / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D000431:Ethanol; D002336:Carnosine; D004247:DNA; D010450:Endopeptidases; D002401:Cathepsin B; D002402:Cathepsin D; D000079:Acetaldehyde