Involvement of UDP-GlcNAc biosynthesis in sexual dysfunctions caused by endocrine disrupting chemicals

UDP-GlcNAc 生物合成参与内分泌干扰化学物质引起的性功能障碍

• 批准号: 11670348
• 负责人: OKABE Toshiko
• 金额: $ 2.18万
• 依托单位: Yokohama City University
• 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-11670348/
• 关键词: male infertility; UDP-Ν-acetylglucosamine; UAP1; AgX1; anti-sperm antibody; GlcNAc kinase; GlcNAc-phosphate deacetyiase; NAG cluster; N-アセチルグルコサミン; 精子運動率; AgX-1; Agx-1; 内分泌かく乱物質

In human and animals, male sexual dysfunctions had been reported recently. It is suggested that the reason for this phenomenon was thought to be the effects of endocrine disrupting chemicals on sex hormone receptors. Human N-acetylglucosamine-1-phosphate uridyltransferase (UAP1) is expressed in testis and sperm tail, especially outer dense fiber and thought to play important function in sexual function. In this study, we found that the antibody against UAP1 was detected more frequently in sperm plasma with impaired sperm motility. Because the primary structure of UAP1 showed the partial homology with several sperm surface proteins, the antibody against UAP1 might prevent the function of UAP1 as well as other sperm surface proteins, and cause the inhibition of various sperm function.Furthermore, GNA1 and AGM1, which encode glucosamine-6-phosphate acetyltransferase and phosphoacetylglucosamine mutase, respectively, and are involved in eukaryotic UDP-GlcNAc biosynthesis as well as UAP1 had been cloned and characterized. Furthermore the enzymes for catabolism of N-acetylglucosamine (GlcNAc) such as GlcNAc kinase and GlcNAc-phosphate deacetylase were identified and characterized.

在人类和动物中，最近报道了男性性功能障碍。有人认为，这种现象的原因被认为是内分泌破坏化学物质对性激素受体的影响。人N-乙酰葡萄糖1-磷酸尿苷转移酶（UAP1）在睾丸和精子尾部（尤其是外部密度纤维）中表达，并被认为在性功能中起重要功能。在这项研究中，我们发现，在精子运动障碍的精子血浆中更频繁地检测到针对UAP1的抗体。由于UAP1的主要结构与多种精子表面蛋白显示部分同源性，因此针对UAP1的抗体可能会阻止UAP1以及其他精子表面蛋白的功能，并引起各种精子功能。分别编码葡萄糖胺-6-磷酸乙酰基转移酶和磷酸乙酰葡萄糖胺突变酶，并参与真核UDP-GLCNAC生物合成以及UAP1，以及UAP1的克隆和表征。此外，还鉴定并表征了N-乙酰葡萄糖（GlcNAC）的分解代谢（GlcNAC），例如GlcNAC激酶和GlcNAC-磷酸脱乙酰基酶的酶。

项目成果

Yamada-Okabe T., Yamada-Okabe H.: "Characterization of the CaNAG3, CaNAG4 and CaNAG6 genes of the pathogenic fungus Candida albicans"(submitted).

Yamada-Okabe T.，Yamada-Okabe H.：“病原真菌白色念珠菌的 CaNAG3、CaNAG4 和 CaNAG6 基因的特征”（已提交）。

Mio T.et al.: "Saccharomyces cerevisiae GNA I, an essential gene encoding a novel acetyltransferase involved in UDP-N-acetylgluocosamine synthesis"J.Biol.Chem. 274. 424-429 (1999)

Mio T.等人：“酿酒酵母 GNA I，编码参与 UDP-N-乙酰葡萄糖胺合成的新型乙酰转移酶的必需基因”J.Biol.Chem。

Mio, T et al: "Saccharomyces cereviaise GNA1, an essential gene encoding a novel acetyltransferse invoved in UDP-N-acetylglucosamine synthesis"Journal of Biological Chemistry. 274(1). 424-429 (1999)

Mio, T 等人：“酿酒酵母 GNA1，一种编码参与 UDP-N-乙酰葡糖胺合成的新型乙酰转移酶的必需基因”生物化学杂志。

Yamada-Okabe T. et al.: "Identification and characterization of the gene for N-acetylglucosamine kinase and N-acetylglucosamine-phosphate deacetylase in the pathogenic fungus Candida albicans"Eur.J.Biochem. 268. 2498-2505 (2001)

Yamada-Okabe T.等：“致病性真菌白色念珠菌中N-乙酰葡糖胺激酶和N-乙酰葡糖胺-磷酸脱乙酰酶基因的鉴定和表征”Eur.J.Biochem。