Production of tumor growth‐inhibiting protein by the neonatal mouse brain: Dependence on intracellular glutamine metabolism
Production of tumor growth‐inhibiting protein by the neonatal mouse brain: Dependence on intracellular glutamine metabolism
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新生小鼠大脑产生肿瘤生长抑制蛋白：依赖于细胞内谷氨酰胺代谢
DOI：
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发表时间：
1987
影响因子：
5.6
通讯作者：
S. Mizuno
中科院分区：
文献类型：
--
作者：
N. Miwa;T. Matsuno;S. Mizuno
我们之前报道过，小鼠大脑在新生阶段而非成年阶段会分泌一种62,000 Da的致癌因子，称为NBCF，它比正常细胞优先抑制恶性细胞的克隆生长和DNA合成。在本研究中，研究了新生小鼠大脑在培养物中产生的 NBCF。向培养基中添加 L-谷氨酰胺可显着促进 NBCF 的产生，且呈浓度依赖性。这种生产似乎是谷氨酰胺特有的，因为 L-谷氨酸、其类似物 DL-α-氨基己二酸、L-天冬酰胺或 L-天冬氨酸或其他氨基酸或维生素没有产生促进作用。在不含 L-谷氨酰胺或含有 6-重氮-5-氧代-L-正亮氨酸（一种谷氨酰胺拮抗剂）或 L-蛋氨酸亚磺酰亚胺（一种谷氨酰胺合成酶抑制剂）的培养基中，NBCF 的产量显着减少。因此，L-谷氨酰胺的细胞外供应、细胞内合成和利用促进了 NBCF 的产生，但不受其脱酰胺形式或同源氨基酸的影响。另一方面，通过向培养基中添加放线菌酮，NBCF 的产生被完全抑制。放线菌素 D 也发挥抑制作用，但不完全，而胞嘧啶 β-D-阿拉伯呋喃糖苷不抑制 NBCF 的产生。这些结果表明，培养产生的 NBCF 与 DNA 复制无关，但主要取决于转录阶段及其后续阶段，部分取决于从预先存在的 mRNA 到蛋白质的翻译阶段。
We previously reported that the mouse brain at the neonatal stage but not at the adult stage secreted a carcinostatic factor of 62,000 Da, termed NBCF, which inhibited clonal growth and DNA synthesis of malignant cells preferentially over those of normal cells. In the present study, NBCF production by the neonatal mouse brain in culture was investigated. Addition of L‐glutamine to the culture medium markedly promoted NBCF production in a concentration‐dependent manner. The production seemed to be specific to glutamine, since no promotive effect was exerted by L‐glutamic acid, its analogue DL‐α‐aminoadipic acid, L‐aspargine, or L‐aspartic acid or by other amino acids or vitamins. NBCF production was markedly reduced in culture medium either devoid of L‐glutamine or containing 6‐diazo‐5‐oxo‐L‐norleucine, a glutamine antagonist, or L‐metionine sulfoximine, an inhibitor of glutamine synthetase. Thus NBCF production was promoted by extracellular supply, intracellular synthesis, and utilization of L‐glutamine but was not affected by its deamidated form or homologue amino acids. On the other hand, NBCF production was completly repressed by addition of cycloheximide to the culture medium. The repressive effect was also exerted by actinomycin D although not completely, whereas cytosine β‐D‐arabinofuranoside did not repress NBCF production. These results indicated that NBCF production by cultivation was independent of DNA replication but dependend mostly on a transcription stage and its following stages and partly on a translation stage from the preexisting mRNA to the protein.
L-谷氨酰胺浓度与大鼠肝癌增殖率呈负相关。
影响因子：
6.1
作者：
Sebolt,JS;Weber,G
通讯作者：
Weber,G