大鼠Dunning R3327G前列腺肿瘤中视黄酸氧化分解代谢的分析

Analysis of the oxidative catabolism of retinoic acid in rat Dunning R3327G prostate tumors.

作者信息

Krekels M D, Zimmerman J, Janssens B, Van Ginckel R, Cools W, Van Hove C, Coene M C, Wouters W

机构信息

Department of Endocrino- and Immunopharmacology, Janssen Research Foundation, Beerse, Belgium.

出版信息

Prostate. 1996 Jul;29(1):36-41. doi: 10.1002/(SICI)1097-0045(199607)29:1<36::AID-PROS5>3.0.CO;2-G.

DOI:10.1002/(SICI)1097-0045(199607)29:1<36::AID-PROS5>3.0.CO;2-G

PMID:8685053

Abstract

We studied the enzymatic characteristics of the oxidative catabolism of retinoic acid (RA) and its inhibition by liarozole-fumarate in homogenates of rat Dunning R3327G prostate tumors. Homogenates of rat liver were used as reference material. Both tumor and liver homogenates were able to catabolize retinoic acid. HPLC analysis revealed only very polar metabolites in tumors, while in the liver both metabolites with intermediate polarity and more polar metabolites were found. Kinetic analysis of retinoic acid catabolism showed a K(m) of 1.7 +/- 0.7 microM and a Vmax of 4.2 +/- 4.4 pmol polar RA metabolites/mg protein/hr for Dunning G tumor homogenates. In liver homogenates a K(m) value of 4.3 +/- 0.5 microM and a Vmax value of 290 +/- 120 pmol polar RA metabolites/mg protein/hr were obtained. Liarozole-fumarate inhibited retinoic acid catabolism in Dunning tumors and liver with IC50 values of 0.26 +/- 0.16 microM and 0.14 +/- 0.05, respectively. The results suggest that rat Dunning R3327G tumors are able to metabolize retinoic acid in a manner similar to that found in rat liver but with a lower metabolizing capacity.

摘要

我们研究了维甲酸（RA）氧化分解代谢的酶学特性及其在大鼠Dunning R3327G前列腺肿瘤匀浆中被富马酸氯苯唑酸抑制的情况。大鼠肝脏匀浆用作参考材料。肿瘤和肝脏匀浆均能够分解代谢维甲酸。高效液相色谱分析显示，肿瘤中仅存在极性很强的代谢产物，而在肝脏中则发现了中等极性代谢产物和极性更强的代谢产物。维甲酸分解代谢的动力学分析表明，Dunning G肿瘤匀浆的米氏常数（K(m)）为1.7±0.7微摩尔，最大反应速度（Vmax）为4.2±4.4皮摩尔极性RA代谢产物/毫克蛋白质/小时。在肝脏匀浆中，米氏常数（K(m)）值为4.3±0.5微摩尔，最大反应速度（Vmax）值为290±120皮摩尔极性RA代谢产物/毫克蛋白质/小时。富马酸氯苯唑酸抑制Dunning肿瘤和肝脏中的维甲酸分解代谢，其半数抑制浓度（IC50）值分别为0.26±0.16微摩尔和0.14±0.05微摩尔。结果表明，大鼠Dunning R3327G肿瘤能够以与大鼠肝脏中相似的方式代谢维甲酸，但代谢能力较低。