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 β1, 2 dimer of rat collagen type I; it was sensitive to digestion by a highly purified collagenease 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. © 1990 Academic Press, Inc.