Acetaldehyde-collagen adducts in CCl4-induced liver injury in rats.
Circulating AC levels as well as antibodies against AC-protein adducts are increased in non-alcoholic liver injury. To identify the adducts, we used rats with CCl4-induced cirrhosis. Liver subcellular fractions were analyzed by immunochemical staining of protein slot blots and of electrophoretically separated proteins, transferred to nitrocellulose, using AC-protein adduct-specific antibodies. One reactive protein of about 200 kD was detected in the liver soluble fraction and in the cytosol of isolated hepatocytes and, to a lesser extent in the liver microsomes of CCl4-treated rats; in control animals, this reactivity was much weaker. The immunopositive AC adduct co-migrated with the beta 1,2 dimer of rat collagen type I; it was sensitive to digestion by a highly purified collagenase and also reacted with anti-rat collagen type I-specific IgG. In addition, comparison of peptides of the CNBr-digested, immunoprecipitated AC adduct with those of rat collagen type I revealed a high degree of similarity. Thus, AC adduct formation occurs in liver injury of non-alcoholic origin, and a target protein appears to be related to collagen type I, most likely the procollagen precursor.
Behrens
U J
UJ
Alcohol Research and Treatment Center, Department of Veterans Affairs, Bronx, New York 10468.
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Bychenok
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Baraona
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Lieber
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CS
D000079:Acetaldehyde / Q000378:metabolism*; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen / Q000302:isolation & purification / Q000378:metabolism*; D003488:Cyanogen Bromide; D008099:Liver / Q000378:metabolism*; D003012:Microbial Collagenase / Q000378:metabolism; D008970:Molecular Weight; D010446:Peptide Fragments / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D010446:Peptide Fragments; D003094:Collagen; D003012:Microbial Collagenase; D000079:Acetaldehyde; D003488:Cyanogen Bromide