INHIBITION OF PROTEIN GLYCOSYLATION AND SELECTIVE CYTO-TOXICITY TOWARD VIRALLY TRANSFORMED FIBROBLASTS CAUSED BY B3-TUNICAMYCIN
INHIBITION OF PROTEIN GLYCOSYLATION AND SELECTIVE CYTO-TOXICITY TOWARD VIRALLY TRANSFORMED FIBROBLASTS CAUSED BY B3-TUNICAMYCIN
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DOI：
10.1111/j.1432-1033.1982.tb07022.x
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发表时间：
1982-01-01
期刊：
影响因子：
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通讯作者：
MAHONEY, WC
中科院分区：
文献类型：
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作者：
DUKSIN, D;SEIBERG, M;MAHONEY, WC
用鸡胚成纤维细胞、小鼠成纤维细胞系（3 T3）和病毒转化的小鼠成纤维细胞系（SV 40 - 3 T3）研究了唯一已知的含有饱和脂肪酸侧链的衣霉素同系物B3-衣霉素的生物学效应。这种同源物抑制N-乙酰葡糖胺1-磷酸盐从UDP-N-乙酰葡糖胺转移到长叶醇磷酸盐，由鸡肝微粒体或培养的小鼠成纤维细胞催化。3-衣霉素也抑制甘露糖纳入鸡或小鼠成纤维细胞合成的糖蛋白。掺入的氨基酸脯氨酸和酪氨酸被抑制B3-衣霉素的程度小于甘露糖的掺入。甘露糖掺入到由病毒转化细胞合成的糖蛋白中被B3-衣霉素抑制到比在非转化系或鸡原代成纤维细胞中实现的程度更高的程度。当将B3-衣霉素作为蛋白质糖基化抑制剂的活性与衣霉素的其他同系物进行比较时，它是最有活性的。该同源物在鸡和小鼠成纤维细胞中以50 ng/ml的浓度以及在转化的小鼠成纤维细胞中以10 ng/ml的浓度引起蛋白质糖基化的完全（> 95%）抑制。当衣霉素同系物的细胞毒活性进行了检查，对非转化和病毒转化的3 T3细胞，它被发现，B3-衣霉素显示出最高的选择性细胞毒性转化细胞。当转化的成纤维细胞（105个细胞/板）用B3-衣霉素（100 ng/ml）处理48小时时，观察到完全细胞死亡。即使用浓度高达500 ng/ml的B3-衣霉素处理，未转化的成纤维细胞的活力和增殖活性也是正常的。B3-衣霉素可能是动物肿瘤生长研究的合适候选药物。
The biological effect of B3-tunicamycin, the only known homologue of tunicamycin which contains a saturated fatty-acid side chain, was examined using chick embryo fibroblasts, a mouse fibroblastic line (3T3) and a virally transformed mouse fibroblastic line (SV40-3T3). This homologue inhibited the transfer of N-acetylglucosamine 1-phophate from UDP-N-acetylglucosamine to dolichyl phosphate, catalyzed by microsomes from chick liver or from cultured mouse fibroblasts. B3-tunicamycin also inhibited the incorporation of mannose into glycoproteins synthesized by chick or mouse fibroblasts. Incorporation of the amino acids proline and tyrosine was inhibited by B3-tunicamycin to a lesser extent than the incorporation of mannose. The mannose incorporation into glycoproteins synthesized by virally transformed cells was inhibited by B3-tunicamycin to a higher degree than what was achieved in the nontransformed lines or in the chick primary fibroblasts. When the activity of B3-tunicamycin as an inhibitor of protein glycosylation was compared to to other homologues of tunicamycin, it was the most active. This homologue caused complete (> 95%) inhibition of protein glycosylation at a concentration of 50 ng/ml in chick and in mouse fibroblasts and at a concentration of 10 ng/ml in transformed mouse fibroblasts. When the cytotoxic activities of tunicamycin homologues were examined on nontransformed and virally transformed 3T3 cells, it was found that B3-tunicamycin displayed the highest selective cytotoxicity toward the transformed cells. When transformed fibroblasts (105 cells/plate) were treated with B3-tunicamycin (100 ng/ml) for 48 h, complete cell death was observed. The viability and the proliferative activity of the nontransformed fibroblast were normal even when treated with concentrations up to 500 ng/ml of B3-tunicamycin. B3-tunicamycin may be a suitable candidate for studies of tumor growth in animals.