Alteration in the regulation of plasma membrane glycoproteins of the hepatocyte during ontogeny.

Alteration in the regulation of plasma membrane glycoproteins of the hepatocyte during ontogeny.
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个体发育过程中肝细胞质膜糖蛋白调节的改变。

DOI:
10.1016/0014-4827(90)90095-r
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发表时间:
1990
影响因子:
3.7
通讯作者:
Bujanover,Y
Bujanover,Y
中科院分区:
医学3区
文献类型:
--
作者:
Petell,JK;Quaroni,A;Hong,WJ;Hixson,DC;Amarri,S;Reif,S;Bujanover,Y

文献摘要

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在肝脏发育过程中,利用单特异性抗体详细检查了四种膜糖蛋白的表达。这些包括去唾液酸糖蛋白受体,肝细胞糖蛋白驻留在窦域,和三个胆小管糖蛋白,亮氨酸氨基肽酶,二肽基肽酶IV,和aMr 110,000糖蛋白表示GP 110。据观察,脱唾液酸糖蛋白受体,GP 110,和二肽基肽酶IV存在于胎儿肝脏中的低量,并在1至3周之间达到成人水平。与此相反,亮氨酸氨肽酶是目前在近成人的金额在18天的胎肝。这些观察结果通过胎鼠和成年大鼠冰冻薄肝切片的间接免疫荧光染色定性证实。此外,在胎肝中,发现亮氨酸氨肽酶不局限于典型的胆小管区域。在蛋白水解抑制剂的存在下,使用洗涤剂溶解的代谢标记肝切碎物提取物进行免疫沉淀研究,结果显示,GP 110在17天胎肝中以Mr110,000和Mr105,000多肽的形式存在,但在妊娠21天时,较大的多肽是主要的合成产物。相反,亮氨酸氨肽酶和二肽基肽酶IV的表观分子量在发展过程中没有改变。使用过量的抗体确定相对合成速率的实验表明,个体发育过程中肝脏中三种胆小管糖蛋白的浓度反映了它们的合成速率。这些结果强调了肝细胞的质膜成分在表达和定位方面发生了巨大的变化,因为肝脏在出生时改变了其生理作用。
The expression of four integral membrane glycoproteins was examined in detail utilizing monospecific antibodies during liver development. These included asialoglycoprotein receptor, a hepatocyte glycoprotein residing in the sinusoidal domain, and three bile canalicular glycoproteins, leucine aminopeptidase, dipeptidyl peptidase IV, and aMr110,000 glycoprotein denoted GP 110. It was observed that asialoglycoprotein receptor, GP 110, and dipeptidyl peptidase IV were present in low amounts in fetal liver and reached adult levels between 1 to 3 weeks. In contrast, leucine aminopeptidase was present in nearly adult amounts in 18-day-old fetal livers. These observations were qualitatively confirmed by indirect immunofluorescent staining of frozen thin liver sections obtained from fetal and adult rats. Further, in fetal livers it was found that leucine aminopeptidase was not localized to typical bile canalicular areas. Immunoprecipitation studies performed in the presence of proteolytic inhibitors using detergent-solubilized extracts of metabolically labeled liver minces revealed that GP 110 was present in low amounts asMr110,000 andMr105,000 polypeptides in 17-day fetal livers but by 21 days of gestation the larger polypeptide was the major synthesis product. Conversely, the apparent molecular weights of leucine aminopeptidase and dipeptidyl peptidase IV were not altered during development. Experiments determining relative rates of synthesis using excess amounts of antibodies showed that the concentrations of the three bile canalicular glycoproteins in liver during ontogeny reflect their rates of synthesis. These results underscore that plasma membrane constituents of the hepatocyte undergo dramatic changes in expression and localization as the liver changes its physiological role at birth.