Evidence that impaired intracellular collagen synthesis reduces proliferation in cultured rat hepatocytes.
Contribution of collagen to cell proliferation was studied in cultured hepatocytes. When alpha,alpha'-dipyridyl, an iron chelator which blocks hydroxylation of prolyl and lysyl residues of procollagen and expression of procollagen mRNA, was added to the medium of rat hepatocytes in primary culture, DNA synthesis of the cells was reduced in a dose-related manner without changes in protein synthesis. The reduction of collagen synthesis was parallel with the changes of DNA synthesis. The addition of P-1894B or minoxidil, which inhibits specifically prolyl hydroxylase or lysyl hydroxylase, respectively, also produced similar results. However, the DNA synthesis was not affected by beta-aminopropionitrile fumarate, which inhibits cross linking in extracellular collagen maturation, nor by purified bacterial collagenase. Intracellular processing of collagen synthesis may be required for proliferation in cultured rat hepatocytes.
Ikeda
H
H
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Ogata
I
I
Fujiwara
K
K
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D000629:Aminopropionitrile / Q000494:pharmacology; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology*; D008297:Male; D008914:Minoxidil / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000880:Anthraquinones; D000629:Aminopropionitrile; D015082:2,2'-Dipyridyl; D008914:Minoxidil; C032958:vineomycin A1; D003094:Collagen; D004247:DNA