Oral ingestion of mannose alters the expression level of deaminoneuraminic acid (KDN) in mouse organs
Oral ingestion of mannose alters the expression level of deaminoneuraminic acid (KDN) in mouse organs
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DOI：
10.1007/s10719-006-6734-z
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发表时间：
2006-07-01
影响因子：
3
通讯作者：
Kitajima, Ken
中科院分区：
文献类型：
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作者：
Go, Shinji;Sato, Chihiro;Kitajima, Ken
脱氨基神经氨酸（KDN）是唾液酸家族的独特成员。我们先前证明，游离KDN是在鳟鱼睾丸中从甘露糖作为其前体糖从头合成的，并且在富含甘露糖的培养基中培养的小鼠B16黑素瘤细胞中细胞内KDN的量增加[Angata等人（1999）J.Biol.Chem.274，22949-56; Angata等人（1999）Biochem. Biophys. Res. Commun. 261，326-31]。在本研究中，我们首先证明了在各种培养的小鼠和人细胞系中甘露糖诱导的细胞内KDN增加。这些结果使我们检查KDN在小鼠器官中的表达是否被外源施用的甘露糖改变。在正常饲养条件下，细胞内游离KDN在肝、脾和肺中以非常低的水平（19-48 pmol/mg蛋白）存在，并且在肾或脑中未检测到。短期（90分钟）和长期（2周）口服甘露糖，导致脾和肺细胞内KDN增加至60-81 pmol/mg蛋白，肾和脑细胞内KDN增加至6.9-18 pmol/mg蛋白;然而，在肝脏中未观察到变化。器官中KDN的水平似乎不仅由KDN 9-磷酸合酶活性决定，还可能受到利用甘露糖6-磷酸作为底物的其他酶以及分解KDN的酶（如KDN-丙酮酸裂解酶）的影响。在血液中，游离KDN的可检测量在口服甘露糖后没有变化。这些结果表明，甘露糖在饮食中影响KDN代谢的各种器官，并提供线索，改变KDN表达在一些肿瘤细胞和老化器官的机制。
Deaminoneuraminic acid (KDN) is a unique member of the sialic acid family. We previously demonstrated that free KDN is synthesized de novo from mannose as its precursor sugar in trout testis, and that the amount of intracellular KDN increases in mouse B16 melanoma cells cultured in mannose-rich media [Angata et al. (1999) J. Biol. Chem. 274, 22949-56; Angata et al. (1999) Biochem. Biophys. Res. Commun. 261, 326-31]. In the present study, we first demonstrated a mannose-induced increase in intracellular KDN in various cultured mouse and human cell lines. These results led us to examine whether KDN expression in mouse organs is altered by exogenously administered mannose. Under normal feeding conditions, intracellular free KDN was present at very low levels (19-48 pmol/mg protein) in liver, spleen, and lung, and was not detected in kidney or brain. Oral ingestion of mannose, both short-term (90 min) and long-term (2 wk), resulted in an increase of intracellular KDN up to 60-81 pmol/mg protein in spleen and lung and 6.9-18 pmol/mg protein in kidney and brain; however, no change was observed in liver. The level of KDN in organs appears not to be determined only by the KDN 9-phosphate synthase activity, but might also be affected by other enzymes that utilize mannose 6-phosphate as a substrate as well as the enzymes that breakdown KDN, like KDN-pyruvate lyase. In blood, the detectable amount of free KDN did not change on oral ingestion of mannose. These findings indicate that mannose in the diet affects KDN metabolism in various organs, and provide clues to the mechanism of altered KDN expression in some tumor cells and aged organs.