Studies on the biological role of N-glycan in the maturation process of neutrophilic cells

N-聚糖在中性粒细胞成熟过程中的生物学作用研究

• 批准号: 11671020
• 负责人: MISAGO Masahiro
• 金额: $ 2.24万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671020/
• 关键词: Asn-linked glycan; neutrophil maturation; deoxynojirimycin; swainsonine; G-CSF receptor

The N-glycan inhibitors such as swainsonine and N-butyldeoxynojirimycin (NB-DN) lead to the biosynthesis of the incomplete N-linked oligosaccharide. The effects of these inhibitors on granulopoiesis was investigated using human bone marrow cells in vitro containing granulocyte colony-stimulating factor (G-CSF). The addition of the inhibitors led to the decrease in the number of mature neutrophils. Swainsonine did not induce apoptosis, but NB-DNJ induced considerable apoptosis. This result indicated that the decrease of mature neutrophils by swainsonine was not because of cell degeneration but the suppression of maturation from myelocytes into neutrophils. In the case of NB-DNJ, it was thought to be because of both apoptosis and maturation suppression. The inhibitors also suppressed the expressions of mRNAs of CCAAT/enhancer binding protein epsilon (C/EBPε) and G-CSF receptor as markers of terminal neutrophil maturation. Furthermore, the effect of NB-DNJ was investigated using all trans retinoic acid (ATRA)-stimulated HL-60 cells as the model of neutrophil differentiation. NB-DNJ suppressed the differentiation of HL-60 and the expression of G-CSF receptor mRNA. In this study, it has been elucidated that the inhibitors of N-linked oligosaccharide synthesis leads to the suppression of terminal neutrophil maturation.

N-聚糖抑制剂如苦马豆素和N-丁基脱氧野尻霉素（NB-DN）导致不完全N-连接寡糖的生物合成。这些抑制剂对粒细胞生成的影响进行了研究，使用人骨髓细胞在体外含有粒细胞集落刺激因子（G-CSF）。添加抑制剂导致成熟中性粒细胞数量减少。苦马豆素不诱导细胞凋亡，但NB-DNJ诱导大量细胞凋亡。这一结果表明，苦马豆素减少成熟的中性粒细胞不是因为细胞变性，而是因为抑制了从骨髓细胞向中性粒细胞的成熟。在NB-DNJ的情况下，它被认为是因为细胞凋亡和成熟抑制。抑制剂还抑制作为终末中性粒细胞成熟标志物的CCAAT/增强子结合蛋白ε（C/EBPε）和G-CSF受体的mRNA表达。此外，使用全反式维甲酸（ATRA）刺激的HL-60细胞作为中性粒细胞分化的模型来研究NB-DNJ的作用。NB-DNJ可抑制HL-60细胞的分化和G-CSF受体mRNA的表达。在这项研究中，已经阐明，N-连接寡糖合成的抑制剂导致终末中性粒细胞成熟的抑制。

项目成果

Junichi Tsukada, Masahiro Misago, et al.: "Constitutive activation of LIL-Stat in adult T-cell leukemia cells"Blood. 90(8). 2715-2718 (2000)

Junichi Tsukada、Masahiro Misago 等人：“成人 T 细胞白血病细胞中 LIL-Stat 的组成型激活”血液。

Masahiro Misago,et al.: "Suppressive Effects of Swainsonine and N-buty l deoxynojirimycin on Human Bone Marrow Neutrophil Maturation"Biochemical and Biophysical Research Communications. 269・1. 219-225 (2000)

Masahiro Misago等人：“苦马豆素和N-丁基脱氧野尻霉素对人骨髓中性粒细胞成熟的抑制作用”生物化学和生物物理研究通讯269·1(2000)。

Oh-Eda M, et al.: "Over expression of the golgi-localized enzyme alphamannosidase IIx in Chinese hamster ovary cells results in conversion of hexamannosyl-N-acetylchitobiose to tetramannosyl-N-acetylchitobiose in the N-glycan processing pathway"Eur J Bioc

Oh-Eda M 等人：“中国仓鼠卵巢细胞中高尔基定位酶 α-甘露糖苷酶 IIx 的过度表达导致 N-聚糖加工途径中的六甘露糖基-N-乙酰壳二糖转化为四甘露糖基-N-乙酰壳二糖”Eur J

Masahiro Misago: "Suppressive Effects of Swainsonine and N-butyldeoxynojirimycin on Human Bone Marrow Neutrophil Maturation"Biochemical and Biophysical Research Communications. 269(1). 219-225 (2000)

Masahiro Misago：“苦马豆素和 N-丁基脱氧野尻霉素对人骨髓中性粒细胞成熟的抑制作用”生物化学和生物物理研究通讯。