Greco S, Hugueny I, George P, Perrin P, Louisot P, Biol M C
Unité INSERM U189 - SDI CNRS, Département de Biochimie, Faculté de Médecine Lyon-Sud, BP 12, 69600 Oullins, France.
Biochem J. 2000 Jan 1;345 Pt 1(Pt 1):69-75.
Previous work has shown an inverse evolution of the rat intestinal glycoprotein sialylation that decreases from birth to weaning and of fucosylation that increases markedly after weaning during postnatal development. At weaning time, an increase in the intestinal level of polyamines (and especially that of spermine) was observed, owing partly to the higher level of spermine found in solid food given to rats at this period in comparison with the level found in milk. To study the role of this polyamine as a possible maturation factor of the glycoprotein glycosylation, suckling rats were treated for 4 days with spermine administered orally. This treatment allowed us to mimic the spermine increase that was observed naturally in rat small intestine after weaning because, in intestines of spermine-treated suckling rats, spermine was the only polyamine to be increased and was at a level similar to that of weaned rats. Spermine treatment did not induce appreciable changes in sialyltransferase activity or in sialylation of the brush-border-membrane glycoproteins. On the contrary, this treatment induced a rise in an alpha-1, 2-fucosyltransferase activity that was regulated at the transcriptional level, but not by its inhibitor (fuctinin), and no change in the availability of substrate (GDP-fucose). As a consequence of the increase in alpha-1,2-fucosyltransferase level and of the decrease in alpha-l-fucosidase level after treatment with spermine, several alpha-1,2-fucoproteins, naturally found in brush border membranes after weaning time, appeared precociously in these membranes after the treatment of the immature suckling rats. These results indicate that spermine is a maturation factor for the fucosylation of intestinal brush-border-membrane glycoproteins but not for their sialylation, and that this polyamine might be implicated in the increased fucosylation naturally occurring at weaning time during postnatal development.
先前的研究表明,大鼠肠道糖蛋白的唾液酸化在出生后至断奶期间呈反向变化,即逐渐减少;而岩藻糖基化则在断奶后显著增加。在断奶时,观察到肠道中多胺水平(尤其是精胺)升高,部分原因是与牛奶中的精胺水平相比,这一时期给予大鼠的固体食物中精胺水平更高。为了研究这种多胺作为糖蛋白糖基化可能的成熟因子的作用,给哺乳大鼠口服精胺,持续处理4天。这种处理使我们能够模拟断奶后大鼠小肠中自然发生的精胺增加,因为在经精胺处理的哺乳大鼠的肠道中,精胺是唯一增加且水平与断奶大鼠相似的多胺。精胺处理并未引起唾液酸转移酶活性或刷状缘膜糖蛋白唾液酸化的明显变化。相反,这种处理导致一种α-1,2-岩藻糖基转移酶活性升高,该酶在转录水平受到调控,但不受其抑制剂(岩藻糖基化抑制剂)的影响,并且底物(GDP-岩藻糖)的可用性没有变化。由于用精胺处理后α-1,2-岩藻糖基转移酶水平升高以及α-1-岩藻糖苷酶水平降低,断奶后自然存在于刷状缘膜中的几种α-1,2-岩藻糖蛋白在未成熟的哺乳大鼠经处理后提前出现在这些膜中。这些结果表明,精胺是肠道刷状缘膜糖蛋白岩藻糖基化的成熟因子,但不是其唾液酸化的成熟因子,并且这种多胺可能与出生后发育过程中断奶时自然发生的岩藻糖基化增加有关。