Free and small peptide-bound [14C]hydroxyproline synthesis in rat liver in vitro in CCl4-induced hepatic fibrosis.
To clarify the process of free and small peptide-bound hydroxyproline synthesis in hepatic fibrogenesis, we measured the in vitro synthesis of [14C]hydroxyproline in the 67% ethanol soluble fraction in rat liver slices, together with hepatic protein-bound [14C]hydroxyproline synthesis. In control rat liver, the amount of free and small peptide-bound [14C]hydroxyproline synthesized was 13.1 +/- 2.6 10(-4) x dpm/g liver/3 hr. In the CCl4-treated rat liver, where the hepatic hydroxyproline content was increased 4.6-fold, the protein-bound [14C]hydroxyproline synthesis was significantly increased 1.5-fold, but free and small peptide-bound [14C]hydroxyproline synthesis was decreased into 70%. There was a significant inverse correlation between free and small peptide-bound [14C]hydroxyproline synthesis, and hepatic hydroxyproline content. These results suggest that the combination of an increase in collagen synthesis and a decrease in free and small peptide-bound [14C]hydroxyproline synthesis contributes to rapid accumulation of collagen in hepatic fibrosis.
Koda
M
M
Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Murawaki
Y
Y
Hirayama
C
C
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000150:complications*; D002403:Cathepsins / Q000378:metabolism; D006909:Hydroxyproline / Q000096:biosynthesis*; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000378:metabolism*; D008297:Male; D003012:Microbial Collagenase / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D051381:Rats
D010455:Peptides; D002403:Cathepsins; D003012:Microbial Collagenase; D006909:Hydroxyproline