ACETALDEHYDE AND MALONDIALDEHYDE REACT TOGETHER TO GENERATE DISTINCT PROTEIN ADDUCTS IN THE LIVER DURING LONG-TERM ETHANOL ADMINISTRATION

Citation
Dj. Tuma et al., ACETALDEHYDE AND MALONDIALDEHYDE REACT TOGETHER TO GENERATE DISTINCT PROTEIN ADDUCTS IN THE LIVER DURING LONG-TERM ETHANOL ADMINISTRATION, Hepatology, 23(4), 1996, pp. 872-880
Citations number
32
Categorie Soggetti
Gastroenterology & Hepatology
Journal title
ISSN journal
02709139
Volume
23
Issue
4
Year of publication
1996
Pages
872 - 880
Database
ISI
SICI code
0270-9139(1996)23:4<872:AAMRTT>2.0.ZU;2-I
Abstract
Acetaldehyde and the lipid peroxidation-derived aldehyde malondialdehy de (MDA), are reactive compounds that are generated during ethanol met abolism in the liver, and both aldehydes have been shown to be capable of binding to proteins and forming stable adducts. Because similar co ncentrations of MDA and acetaldehyde can coexist in the liver during e thanol oxidation, protein adduct formation in the presence of both of these aldehydes was studied under both in vitro and in vivo conditions , When proteins were incubated in the presence of both MDA and acetald ehyde, MDA caused a marked and concentration-dependent increase in the stable binding of acetaldehyde to proteins, Maximum stimulation of bi nding occurred at approximately a fourfold molar excess of MDA relativ e to acetaldehyde when concentrations of 1.0 mmol/L and 0.1 mmol/L wer e tested. The formation of highly fluorescent product or products was associated with the MDA stimulation of acetaldehyde binding, indicatin g that new and distinct products were being generated. These hybrid ad ducts of MDA and acetaldehyde have been designated as MAA adducts, An affinity-purified polyclonal antibody was produced that specifically r ecognized MAA epitopes on proteins and did not cross-react with carrie r proteins or proteins modified with either acetaldehyde or MDA alone. A quantitative competitive enzyme-linked immunosorbent assay (ELISA) was developed and detected the presence of MAA-modified proteins in li ver cytosol hom ethanol-fed rats but not in pair-fed controls. Quantif ication of the data from the competitive ELISA indicated the presence of approximately 75 pmoles protein-bound MAA per milligram liver cytos ol proteins of the ethanol-fed animals. These results indicate that ac etaldehyde and MDA can react together in a synergistic manner and gene rate hybrid adducts (MAA-adducts) and further suggest that MAA adducts may represent a major species of adducts formed in the liver during e thanol metabolism in vivo.