Ogier-Denis E, Trugnan G, Sapin C, Aubery M, Codogno P
Institut National de la Santé et de la Recherche Médicale (INSERM) U. 180, UFR Biomédicale des Saints-Pères, Paris, France.
J Biol Chem. 1990 Apr 5;265(10):5366-9.
1-Deoxymannojirimycin (dMM), a specific alpha-mannosidase I inhibitor, completely blocks the conversion of Man9-8GlcNAc2 into Man7-5-GlcNAc2 in both differentiated and undifferentiated human adenocarcinoma HT-29 cells. Besides this well known effect on N-glycan trimming, we describe here a novel effect of this inhibitor on the D-[2-3H]mannose uptake that is exclusively observed in differentiated intestinal cells, i.e. cells that display a functional apical brush border membrane. This inhibition of D-[2-3H]mannose uptake was shown to be dose-dependent and reversible. Moreover, using microsomal fractions we showed that this effect depends only on the integrity of the brush border and is unrelated to the classical inhibitory effect of dMM on N-glycan processing. Furthermore, another N-glycan trimming inhibitor 1-deoxynojirimycin, an epimer of dMM, did not interfere with D-[2-3H]mannose uptake. This observation was in good agreement with the specificity of the effect induced by dMM. These results demonstrate a novel effect of dMM on highly differentiated intestinal cells and suggest that a carrier-mediated mannose transport could exist in those cells. Such an interaction between cell morphology and the biological effect of dMM should lead to a careful use of drugs acting on N-glycan processing.
1-脱氧甘露基野尻霉素（dMM）是一种特异性的α-甘露糖苷酶I抑制剂，在分化和未分化的人腺癌HT-29细胞中，它能完全阻断Man9-8GlcNAc2向Man7-5-GlcNAc2的转化。除了这种对N-聚糖修剪的众所周知的作用外，我们在此描述了该抑制剂对D-[2-³H]甘露糖摄取的一种新作用，这种作用仅在分化的肠细胞中观察到，即那些具有功能性顶端刷状缘膜的细胞。D-[2-³H]甘露糖摄取的这种抑制作用显示出剂量依赖性且是可逆的。此外，使用微粒体组分，我们表明这种作用仅取决于刷状缘的完整性，与dMM对N-聚糖加工的经典抑制作用无关。此外，另一种N-聚糖修剪抑制剂1-脱氧野尻霉素（dMM的差向异构体）不干扰D-[2-³H]甘露糖的摄取。这一观察结果与dMM诱导的作用的特异性高度一致。这些结果证明了dMM对高度分化的肠细胞具有新作用，并表明在这些细胞中可能存在载体介导的甘露糖转运。dMM的细胞形态与生物学效应之间的这种相互作用应该促使人们谨慎使用作用于N-聚糖加工的药物。
