Inhibition of collagen hydroxylation by 2,7,8-trihydroxyanthraquinone in embryonic-chick tendon cells.
Prolyl 4-hydroxylase (EC 1.14.11.2) is an essential enzyme in the post-translational modification of collagen. Inhibitors of this enzyme are of potential interest for the treatment of diseases involving excessive deposition of collagen. 2,7,8-Trihydroxyanthraquinone (THA) is an effective inhibitor of prolyl 4-hydroxylase by virtue of its ability to compete with the co-substrate 2-oxoglutarate (Ki = 40.3 microM). Using a simple and reproducible assay for collagen hydroxylation, we show that THA inhibits the hydroxylation of collagen in embryonic-chick tendon cells in short-term culture, with an IC50 value (concn. giving 50% inhibition) of 32 microM. In comparison, the ethyl ester of 3,4-dihydroxybenzoic acid has an IC50 value of 0.1 mM against collagen hydroxylation by chick tendon cells, whereas its Ki versus isolated prolyl 4-hydroxylase is 49 microM.
Franklin
T J
TJ
ICI Pharmaceuticals, Macclesfield, Cheshire, U.K.
Hitchen
M
M
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D003094:Collagen; D062385:Hydroxybenzoates / Q000494:pharmacology; D006900:Hydroxylation; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors*; D013710:Tendons / Q000187:drug effects / Q000201:enzymology*
D000880:Anthraquinones; D062385:Hydroxybenzoates; C018063:ethyl protocatechuate; C051323:2,7,8-trihydroxyanthraquinone; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase