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完整大鼠体内微量去唾液酸胎球蛋白和去唾液酸血清类黏蛋白的肝摄取与降解

Hepatic uptake and degradation of trace doses of asialofetuin and asialoorosomucoid in the intact rat.

作者信息

Charlwood P A, Regoeczi E, Hatton M W

出版信息

Biochim Biophys Acta. 1979 Jun 1;585(1):61-70. doi: 10.1016/0304-4165(79)90325-8.

DOI:10.1016/0304-4165(79)90325-8
PMID:87227
Abstract

Asialoorosomucoid and asialofetuin were prepared by using sialidase, which was removed chromatographically before the proteins were labelled with radioactive iodine. After intravenous administration of a small amount oa asialoglycoprotein (3--4 microgram/100 g body wt.) protein-bound and non-protein radioactivities in plasmas and livers of rats were determined at intervals over a period of 30 min. Transfer of either tracer protein from plasma to liver was almost complete in 5 min. Proteolysis of asialofetuin was evident very shortly thereafter, but degradation of asialoorosomucoid commenced after a significant delay and was initially slow relative to that of asialofetuin. Studies in vitro with crude hepatic lysosomal enzyme preparations indicated that asialoorosomucoid was less readily digested than asialofetuin, and that desialylation of orosomucoid or fetuin did not noticeably increase the susceptibility of these proteins to protease action. Proteolysis of asialofetuin was also demonstrable in liver homogenates in conditions under which albumin and asialotransferrin were stable. A generalized mathematical model was devised to represent the uptake and degradation of asialoglycoproteins by the liver. The theoretical assumptions that gave the best fits with experiment are outlined and discussed.

摘要

通过使用唾液酸酶制备去唾液酸糖蛋白和去唾液酸胎球蛋白,在蛋白质用放射性碘标记之前,通过色谱法去除唾液酸酶。静脉注射少量去唾液酸糖蛋白(3 - 4微克/100克体重)后,在30分钟内每隔一段时间测定大鼠血浆和肝脏中与蛋白质结合的放射性和非蛋白质放射性。示踪蛋白从血浆转移到肝脏在5分钟内几乎完成。此后不久,去唾液酸胎球蛋白的蛋白水解就很明显,但去唾液酸糖蛋白的降解在显著延迟后才开始,并且相对于去唾液酸胎球蛋白最初较慢。用粗制肝溶酶体酶制剂进行的体外研究表明,去唾液酸糖蛋白比去唾液酸胎球蛋白更不易被消化,并且血清类黏蛋白或胎球蛋白的去唾液酸化并未显著增加这些蛋白质对蛋白酶作用的敏感性。在白蛋白和去唾液酸转铁蛋白稳定的条件下,在肝匀浆中也可证明去唾液酸胎球蛋白的蛋白水解。设计了一个通用的数学模型来表示肝脏对去唾液酸糖蛋白的摄取和降解。概述并讨论了与实验最吻合的理论假设。

相似文献

1
Hepatic uptake and degradation of trace doses of asialofetuin and asialoorosomucoid in the intact rat.完整大鼠体内微量去唾液酸胎球蛋白和去唾液酸血清类黏蛋白的肝摄取与降解
Biochim Biophys Acta. 1979 Jun 1;585(1):61-70. doi: 10.1016/0304-4165(79)90325-8.
2
Elimination of asialofetuin and asialoorosomucoid by the intact rat. Quantitative aspects of the hepatic clearance mechanism.完整大鼠对去唾液酸胎球蛋白和去唾液酸血清类黏蛋白的清除。肝脏清除机制的定量研究。
Biochim Biophys Acta. 1978 Jul 3;541(3):372-84. doi: 10.1016/0304-4165(78)90196-4.
3
Uptake and degradation of 125I-labeled rat asialoorosomucoid by the perfused rat liver.灌注大鼠肝脏对125I标记的大鼠去唾液酸血清类黏蛋白的摄取与降解
Biochim Biophys Acta. 1984 Mar 22;798(1):14-20. doi: 10.1016/0304-4165(84)90004-7.
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In vivo quantification of receptor-mediated uptake of asialoglycoproteins by rat liver.大鼠肝脏对去唾液酸糖蛋白受体介导摄取的体内定量研究。
J Biol Chem. 1983 Jan 25;258(2):990-4.
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Interaction of hepatic asialoglycoprotein receptor with asialoorosomucoid and galactolyzed lysosomal alpha-glucosidase.
Biochim Biophys Acta. 1986 Sep 4;883(2):306-12. doi: 10.1016/0304-4165(86)90323-5.
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Kinetics of internalization and degradation of asialo-glycoproteins in isolated rat hepatocytes.去唾液酸糖蛋白在分离的大鼠肝细胞中的内化和降解动力学
Eur J Cell Biol. 1980 Dec;23(1):104-9.
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Asialoglycoprotein receptor is uninvolved in clearing intact glycoproteins from rat blood.去唾液酸糖蛋白受体不参与清除大鼠血液中的完整糖蛋白。
Am J Physiol. 1983 Mar;244(3):G247-53. doi: 10.1152/ajpgi.1983.244.3.G247.
8
Effect of leupeptin on the intracellular degradation of asialofetuin in isolated rat hepatocytes.亮抑酶肽对离体大鼠肝细胞中去唾液酸胎球蛋白细胞内降解的影响。
Acta Biol Med Ger. 1981;40(10-11):1599-602.
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Diacytosis of asialoglycoprotein in isolated hepatocytes is dependent on the structure of ligand and cellular distribution of the receptors.分离的肝细胞中去唾液酸糖蛋白的双胞饮作用取决于配体的结构和受体的细胞分布。
Biochim Biophys Acta. 1989 Dec 14;1014(3):229-34. doi: 10.1016/0167-4889(89)90217-6.
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Hepatic asialoglycoprotein receptor-mediated binding of human polymeric immunoglobulin A.肝去唾液酸糖蛋白受体介导的人聚合免疫球蛋白A的结合
Hepatology. 1989 Feb;9(2):229-34. doi: 10.1002/hep.1840090211.

引用本文的文献

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Biodistributions of air-filled albumin microspheres in rats and pigs.大鼠和猪体内充气白蛋白微球的生物分布。
Biochem J. 1994 Apr 15;299 ( Pt 2)(Pt 2):437-43. doi: 10.1042/bj2990437.
2
Use of radioactive glucosamine in the perfused rat liver to prepare alpha 1-acid glycoprotein (orosomucoid) with 3H- or 14C-labelled sialic acid and N-acetylglucosamine residues.在灌注大鼠肝脏中使用放射性葡糖胺来制备带有3H或14C标记的唾液酸和N-乙酰葡糖胺残基的α1-酸性糖蛋白(血清类粘蛋白)。
Biochem J. 1982 Apr 1;203(1):141-8. doi: 10.1042/bj2030141.
3
Partial resialylation of human asialotransferrin type 3 in the rat.
大鼠体内人去唾液酸转铁蛋白3型的部分再唾液酸化
Proc Natl Acad Sci U S A. 1982 Apr;79(7):2226-30. doi: 10.1073/pnas.79.7.2226.
4
Two populations of prelysosomal structures transporting asialoglycoproteins in rat liver.大鼠肝脏中转运去唾液酸糖蛋白的两种前溶酶体结构群体。
Proc Natl Acad Sci U S A. 1984 May;81(10):2995-9. doi: 10.1073/pnas.81.10.2995.
5
Cell surface distribution and intracellular fate of asialoglycoproteins: a morphological and biochemical study of isolated rat hepatocytes and monolayer cultures.去唾液酸糖蛋白的细胞表面分布及细胞内命运:对分离的大鼠肝细胞和单层培养物的形态学与生物化学研究
J Cell Biol. 1982 Mar;92(3):634-47. doi: 10.1083/jcb.92.3.634.
6
Galactose-specific recognition system of mammalian liver: receptor distribution on the hepatocyte cell surface.哺乳动物肝脏的半乳糖特异性识别系统:肝细胞表面的受体分布
J Cell Biol. 1981 Sep;90(3):687-96. doi: 10.1083/jcb.90.3.687.
7
Three types of human asialo-transferrin and their interactions with the rat liver.
Biochem J. 1979 Nov 15;184(2):399-407. doi: 10.1042/bj1840399.