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从大鼠肝细胞原代培养物中鉴定前列腺素E代谢产物。

Identification of prostaglandin E metabolites from primary cultures of rat hepatocytes.

作者信息

Okumura T, Nakayama R, Sago T, Saito K

出版信息

Biochim Biophys Acta. 1985 Nov 14;837(2):197-207.

PMID:4052448
Abstract

Primary cultured rat hepatocytes were shown to bind to prostaglandins E1, E2, D2 and F2 alpha and then rapidly degrade at 37 degrees C. 6-Ketoprostaglandin F1 alpha and thromboxane B2, which are inactive metabolites of prostaglandin I2 and thromboxane A2, respectively, bound less effectively to the cells and were not degraded. Incubation of hepatocytes with 3H-labeled prostaglandins, treatment of the cells at an acidic pH, and analysis of the acid solution by thin-layer chromatography, showed that the radioactive material was bound to the cell surface and consisted of intact prostaglandin and its metabolites. The metabolites of prostaglandin E that accumulated in the culture medium were purified by silicic acid column and silica gel thin-layer chromatographies, and analyzed by gas chromatography-mass spectrometry. Prostaglandins E1 and E2 gave exactly the same metabolites, which were identified as dinorprostaglandin E1 and tetranorprostaglandin E1, representing products of beta-oxidation. These data suggest that part of the carboxyl side chain of prostaglandins, but not of inactive metabolites, was eliminated by a beta-oxidation system in the hepatocytes, while the rest of the molecule was not degraded appreciably and was rapidly transferred to the outside of the cells.

摘要

原代培养的大鼠肝细胞被证明能与前列腺素E1、E2、D2和F2α结合,然后在37℃迅速降解。6-酮前列腺素F1α和血栓素B2分别是前列腺素I2和血栓素A2的无活性代谢产物,它们与细胞的结合效率较低且不会被降解。用3H标记的前列腺素孵育肝细胞,在酸性pH下处理细胞,并通过薄层色谱分析酸性溶液,结果表明放射性物质与细胞表面结合,且由完整的前列腺素及其代谢产物组成。通过硅酸柱和硅胶薄层色谱法对培养基中积累的前列腺素E的代谢产物进行纯化,并通过气相色谱-质谱联用仪进行分析。前列腺素E1和E2产生完全相同的代谢产物,这些代谢产物被鉴定为二去甲前列腺素E1和四去甲前列腺素E1,代表β-氧化产物。这些数据表明,前列腺素羧基侧链的一部分(而非无活性代谢产物的羧基侧链)在肝细胞中通过β-氧化系统被消除,而分子的其余部分没有明显降解,并迅速转移到细胞外。

相似文献

1
Identification of prostaglandin E metabolites from primary cultures of rat hepatocytes.从大鼠肝细胞原代培养物中鉴定前列腺素E代谢产物。
Biochim Biophys Acta. 1985 Nov 14;837(2):197-207.
2
Metabolism of prostaglandins D2 and F2 alpha in primary cultures of rat hepatocytes.大鼠肝细胞原代培养物中前列腺素D2和F2α的代谢
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J Biochem. 1984 Aug;96(2):429-36. doi: 10.1093/oxfordjournals.jbchem.a134854.
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Prostaglandin E1 binding protein on the surface of primary cultured hepatocytes.原代培养肝细胞表面的前列腺素E1结合蛋白。
Biochem Int. 1987 Mar;14(3):443-9.
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Kinetics of prostaglandin E metabolism in isolated hepatocytes.分离肝细胞中前列腺素E代谢的动力学
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Effect of prostaglandins and their analogues on hormone-stimulated glycogenolysis in primary cultures of rat hepatocytes.前列腺素及其类似物对大鼠肝细胞原代培养物中激素刺激的糖原分解的影响。
Biochim Biophys Acta. 1988 Feb 4;958(2):179-87. doi: 10.1016/0005-2760(88)90175-0.
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Studies on synthesis and degradation of eicosanoids by rat hepatocytes in primary culture.原代培养大鼠肝细胞中类二十烷酸的合成与降解研究。
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9-Hydroxyprostaglandin dehydrogenase in rat kidney cortex converts prostaglandin I2 into 15-keto-13,14-dihydro 6-ketoprostaglandin E1.大鼠肾皮质中的9-羟基前列腺素脱氢酶将前列腺素I2转化为15-酮-13,14-二氢6-酮前列腺素E1。
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Species differences in circulating prostaglandin metabolites. Relevance for the assay of prostaglandin release.
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Metabolism of prostaglandins, prostaglandin analogs and thromboxane B2 by lung and liver microsomes from pregnant rabbits.孕兔肺和肝微粒体对前列腺素、前列腺素类似物及血栓素B2的代谢
Biochim Biophys Acta. 1979 Dec 18;575(3):335-49. doi: 10.1016/0005-2760(79)90102-4.

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