The effects of acetaldehyde in vitro on proteasome activities and its potential involvement after alcoholization of rats by inhalation of ethanol vapours.
OBJECTIVE
Some models of chronic ethanol administration resulted in decreased proteasome activities. The mechanisms still remain speculative. In the present study, we tested another model of alcoholization with high blood alcohol levels (BALs) and high acetaldehyde fluxes as well as the in vitro effect of acetaldehyde on proteasome. Methods/


RESULTS
Ethanol vapour chronically inhaled by adult Wistar rats up to a specific protocol, can reach high BALs (200 mg/dl) with significant circulating acetaldehyde levels. After 4 weeks of ethanol intoxication, although cytochrome CYP2E1 was increased, liver lipid peroxidation remained unchanged when protein carbonyls augmented selectively for high molecular weight with a decrease of the proteasome activities in ethanol rats. Several aldehydes inhibit proteasome function; we specifically explored the effects of acetaldehyde, the first alcohol metabolite. Adduction of acetaldehyde in vitro to cytosolic proteins inhibits proteasome in a dose-dependent manner. Acetaldehyde adducted to purified proteasome also exhibits a decrease in its activities. Furthermore, an acetaldehyde-adducted protein, i.e. bovine serum albumin (BSA) is less degraded than a native BSA by purified proteasome. These findings suggest that acetaldehyde, if overproduced, can inhibit proteasome activities and reduce the proteolysis of acetaldehyde-adducted proteins.


CONCLUSIONS
Our study, for the first time, provided the evidence that acetaldehyde by itself inhibits proteasome activities. As the chronic inhalation model used in this study is not associated with an overt lipid peroxidation, one can suggest that high BALs and their subsequent high acetaldehyde fluxes contribute to impairment of proteasome function and accumulation of carbonylated proteins. This early phenomenon may have relevance in experimental alcohol liver disease.
Laboratoire de Recherches Biomédicales sur l'Alcoolisme, Université René Descartes 45, Biomedical Research Centre, rue des Saints-Pères, 75270 Paris, Cedex 06, France. Helene.Rouach@univ-paris5.fr
Hélène
H
Rouach
Evelyne
E
Andraud
Gilles
G
Aufrère
Françoise
F
Beaugé
D000079:Acetaldehyde / Q000633:toxicity*; D000280:Administration, Inhalation; D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008108:Liver Diseases, Alcoholic / Q000503:physiopathology; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D061988:Proteasome Inhibitors; D051381:Rats; D017208:Rats, Wistar
D061988:Proteasome Inhibitors; D000431:Ethanol; D046988:Proteasome Endopeptidase Complex; D000079:Acetaldehyde