Hepatic uptake and metabolism of chylomicron retinyl esters: probable role of plasma membrane/endosomal retinyl ester hydrolases.

Hepatic uptake and metabolism of chylomicron retinyl esters: probable role of plasma membrane/endosomal retinyl ester hydrolases.
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DOI:
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发表时间:
1995-07
影响因子:
6.5
通讯作者:
E. Harrison;M. Gad;A. Ross
E. Harrison;M. Gad;A. Ross
中科院分区:
生物学2区
文献类型:
--
作者:
E. Harrison;M. Gad;A. Ross

文献摘要

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先前的研究表明,存在中性和酸性,胆汁盐非依赖性视黄酯水解酶与质膜和内体组分的大鼠肝匀浆。在目前的研究中,乳糜微粒含有氚标记的视黄酯静脉注射到大鼠,以研究视黄酯的初始代谢过程中和后摄取到肝脏。在乳糜微粒注射后的不同时间,获得血浆,将肝脏匀浆并进行分析性亚细胞分级。标记的视黄酯从血浆中迅速清除(半衰期约为10 min),并出现在肝脏中。在肝脏内,标记首先出现在质膜/内体组分中,这些组分也富含中性和酸性、胆汁盐非依赖性视黄酯水解酶活性。在任何时候标记的酯与富含溶酶体的馏分显着相关。相反,似乎标记的酯被水解和/或转移到富含内质网的组分中。这些研究证明了新递送的视黄酯和胆汁盐非依赖性视黄酯水解酶活性的共定位,因此表明这些酶在乳糜微粒视黄酯的初始肝脏代谢中可能发挥作用。这一结论进一步得到质膜/内体组分在体外催化乳糜微粒残余视黄酯水解的观察结果的支持。
Previous studies have indicated the presence of both neutral and acid, bile salt-independent retinyl ester hydrolases associated with plasma membrane and endosome fractions of rat liver homogenates. In the present studies, chylomicrons containing tritium-labeled retinyl esters were injected intravenously into rats in order to study the initial metabolism of retinyl esters during and after uptake into the liver. At various times after chylomicron injection, plasma was obtained and the liver was homogenized and subjected to analytical subcellular fractionation. Labeled retinyl esters were rapidly cleared from plasma (half-time approximately 10 min) and appeared in the liver. Within the liver, label first appeared in plasma membrane/endosomal fractions that were also enriched in both neutral and acid, bile salt-independent retinyl ester hydrolase activities. At no time were the labeled esters significantly associated with fractions enriched in lysosomes. Rather, it appeared that the labeled esters were hydrolyzed and/or transferred to fractions enriched in endoplasmic reticulum. These studies demonstrate the co-localization of newly delivered retinyl esters and bile salt-independent retinyl ester hydrolase enzyme activities and thus, suggest a probable role for these enzymes in the initial hepatic metabolism of chylomicron retinyl esters. This conclusion was further supported by the observation that plasma membrane/endosomal fractions were active in catalyzing the hydrolysis of chylomicron remnant retinyl esters in vitro.