Inhibition of prolyl hydroxylase activity and collagen biosynthesis by the anthraquinone glycoside, P-1894B, an inhibitor produced by Streptomyces albogriseolus |
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Authors: | T Ishimaru T Kanamaru T Takahashi K Ohta H Okazaki |
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Affiliation: | Microbiological Research Laboratories, Central Research Dvision, Takeda Chemical Industries, Ltd., Osaka 532, Japan |
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Abstract: | P-1894B, a potent prolyl hydroxylase inhibitor produced by Streptomyces albogriseolus subsp. No. 1894, inhibited about 50% of the activity of purified chick embryo prolyl hydroxylase at a concentration of 2.2 x 10(-6) M. The inhibition was noncompetitive with respect to (Pro-Pro-Gly)5 with a Ki of 1.8 x 10(-6)M. When excess amounts of ferrous ions or ascorbate were added to the reaction mixture, the inhibition was slightly reversed. P-1894B at a dose of 0.15 mg/kg reduced the hydroxylation of peptidyl proline and caused a significant inhibition of collagen biosynthesis in the uterus of the immature rat stimulated by the administration of estradiol-17 beta. |
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Keywords: | Author to whom all correspondence should be addressed. |
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