The Effects of Acetaldehyde in Vitro on Proteasome Activities and Its Potential Involvement After Alcoholization of Rats by Inhalation of Ethanol Vapours

Abstract

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.

Modification of mouse A2M B (620-792) and A2M N (168-230) by malondialdehyde and acetaldehyde attenuates the proteinase and TGF-β1 binding ability of A2MB

“…The enhanced inhibition of trypsin activity by MAA‐A2M B might be due to the fact that trypsin may not be able to recognize its substrate after MAA‐adduct formation at lysine and arginine residues. The previous work of Rouach et al [21] substantiate our finding wherein the authors have shown that the aldehyde‐adducted proteins did not appear to be good proteolytic substrates for proteasome. They have reported that modification of BSA with acetaldehyde, MDA or both, delayed the degradation of BSA by proteasome in vitro [21].…”

Proteasome inhibitor model of Parkinson's disease in mice is confounded by neurotoxicity of the ethanol vehicle

“…Another study found the same to be true in the 6‐OHDA model 22. One potential explanation for this effect could be the decrease in proteasome function due to ethanol and its metabolite acetaldehyde 23. In a microarray analysis in which cortical neurons were treated with ethanol for 5 consecutive days, the expression of several genes involved in the UPS, including the α and β subunits of the 20S proteasome, decreased 24…”

The proteasomal system

“…Acetaldehyde inhibits the proteasome in a dose dependent manner both added to purified proteasome and in the form of acetaldehyde-protein adduct (Rouach et al, 2005). Malondialdehyde, another product of lipid peroxidation, and acetaldehyde are able to react with proteins in a synergistic manner.…”