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Regulation and roles of the expression of milk fat globule-characteristic gangliosides in murine mammary gland.

小鼠乳腺乳脂肪球特征神经节苷脂表达的调控和作用。

基本信息

批准号：
08680646
负责人：
IWAMORI Masao
金额：
$ 1.6万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

I performed the experiments using primary cultuted cells and SV-40A255-immortalized cells of murine mammary gland to clarify the mechanism and roles of the expression of milk fat globule-characteristic carbohydrate chains during the periods of pregnancy and lactation. The primary cultured cells were maintained in the basal medium containing cortisol and epidermal growth factor, and were found to be initiated the secretion of milk by addition of prolactin in the basal medium. Synthesis of GD1alpha ganglioside was simultaneously obserbed as an event associated with the secretion of milk under stimulation with prolactin, and was found to be trigered by activations of GM1balpha2-6 sialyltransferase and ceramide lactoside beta1-4N-acetylgalactosaminyltransferase. Also, cholesterol sulfotransferase was highly activated in the cells with secretion of milk, but it was found to be induced by stimulation with epidermal growth factor alone, indicating that the induction of cholesterol sulfotransf … More erase is associated with the growth of mammary epithelial cells. In the case of immortalized cells, the induction of cholesterol sulfotrasferase was observed under stimulation of epidermal growth factor, but production of milk fat grobule, as well as synthesis of GD1alpha, was not observed under the same condition as that for primary cultured cells. The enzuymes thus regulated during the process of milk secretion were found to be controled at the translational level. Then, I invertigated the possible roles of cholesterol sulfate and GD1alpha ganglioside. From the observation that cholesterol sulfate was distributed in the epithelial cells of gastrointestinal tract under the duodenum, where was exposed to the pancreatic digestive enzymes, it was expected to protect the cells from the action of digestive enzymes. As was expected, cholesterol sulfate was found to possess the inhibitory activity toward several proteases, DNase and glycosidases, and one of the major function of cholesterol sulfate in the epithelial cells of mammary gland was found to protect the cells from tissue injury with several enzymes screted during the production of milk. On the other hand, GD1alpha gangloside as the major negatively charged lipids in the fat globule membrane was clarified to be the receptor molecules for toxins from Cl.botulinum type A and type E,and Cl.tetani, indicating that it fuction to protect neonates from the bacterial infections. Less

我利用小鼠乳腺原代培养细胞和SV-40A255永生化细胞进行了实验，以阐明妊娠和哺乳期乳脂肪球特征碳水化合物链表达的机制和作用。将原代培养的细胞维持在含有皮质醇和表皮生长因子的基础培养基中，并且发现通过在基础培养基中添加催乳素来启动乳汁分泌。 GD1α神经节苷脂的合成同时被观察为与催乳素刺激下的乳汁分泌相关的事件，并且被发现是由GM1bα2-6唾液酸转移酶和神经酰胺乳糖苷β1-4N-乙酰半乳糖胺基转移酶的激活引发的。此外，胆固醇磺基转移酶在分泌乳汁的细胞中高度激活，但发现它是通过单独用表皮生长因子刺激来诱导的，表明胆固醇磺基转移酶的诱导与乳腺上皮细胞的生长有关。在永生化细胞的情况下，在表皮生长因子的刺激下观察到胆固醇磺基转移酶的诱导，但在与原代培养细胞相同的条件下未观察到乳脂球的产生以及GD1α的合成。发现在乳汁分泌过程中如此调节的酶是在翻译水平上受到控制的。然后，我探究了硫酸胆固醇和 GD1α 神经节苷脂的可能作用。观察发现，硫酸胆固醇分布在十二指肠下胃肠道的上皮细胞中，这些细胞暴露于胰腺消化酶的作用下，预计它可以保护细胞免受消化酶的作用。正如所料，硫酸胆固醇被发现对多种蛋白酶、DNA酶和糖苷酶具有抑制活性，硫酸胆固醇在乳腺上皮细胞中的主要功能之一是通过在产奶过程中分泌的多种酶来保护细胞免受组织损伤。另一方面，GD1α神经节苷脂作为脂肪球膜中主要带负电荷的脂质，被阐明是A型和E型肉毒杆菌以及破伤风杆菌毒素的受体分子，表明其具有保护新生儿免受细菌感染的作用。较少的