Inhibition of prolyl hydroxylase activity and collagen biosynthesis by fibrostatin C, a novel inhibitor produced by Streptomyces catenulae subsp. griseospora No. 23924.
Fibrostatin C, a novel prolyl hydroxylase inhibitor produced by Streptomyces catenulae subsp. griseospora No. 23924, inhibited the activity of purified chick embryo prolyl hydroxylase by about 50% at a concentration of 2.9 x 10(-5) M. The inhibition was mixed type with respect to (Pro-Pro-Gly)5 with a Ki of 2.1 x 10(-5) M. When an excess of ferrous ions or ascorbate was added to the reaction mixture, the inhibition was negligibly or slightly reversed, respectively. Fibrostatin C, when administered intraperitoneally at 1 mg/kg/day or orally at about 100 mg/kg/day as a dietary admixture, significantly inhibited estradiol-17 beta stimulated collagen biosynthesis in the uterus of the immature rat.
Ishimaru
T
T
Central Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Kanamaru
T
T
Takahashi
T
T
Okazaki
H
H
D000818:Animals; D003094:Collagen / Q000096:biosynthesis*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D009285:Naphthoquinones / Q000494:pharmacology*; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013302:Streptomyces / Q000378:metabolism*
D009285:Naphthoquinones; D004958:Estradiol; D003094:Collagen; C058033:fibrostatin C; D011393:Procollagen-Proline Dioxygenase; D003545:Cysteine