Search for the food derived materials which regulate the expression of cystine/glutamate transporter and its regulatory mechanism.

寻找调节胱氨酸/谷氨酸转运蛋白表达的食源性物质及其调控机制。

• 批准号: 17580103
• 负责人: SATO Hideyo
• 金额: $ 2.3万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17580103/
• 关键词: cystine; glutamate; transporter; glutathione; amino acid; redox; polyphenol; flavonoid

Cystine/glutamate transporter (xCT) is an exchange agency for anionic amino acids with highly specificity for the anionic form of cystine and glutamate. This transporter is known to contribute to the maintenance of intracellular glutathione levels in many types of mammalian cells in culture. The activity of this transporter is induced by various stimuli including electrophilic agents, oxidative stress, cytokines and bacterial lipopolysaccharide. However, it has remained unclear whether any materials derived from food have effects on the expression of xCT and intracellular glutathione. In this study, we focused on flavonoids and searched various flavonoids which have effects on the expression of xCT and intracellular glutathione using a mouse islet cell line, βTC3 cells. In these cells, intracellular glutathione was significantly increased by the addition of quercetin in a dose- and time-dependent manner. In addition to this flavonoid, rhamnetin, isorhamnetin, luteolin, fisetin showed similar effects. These flavonoids also induced the activity of cystine uptake mediated by xCT. On the other hand, Kaempferol, myricetin, quercetagetin, isoquercitrin, morin, apigenin, taxifolin did not increase the intracellular glutathione inβTC3 cells. These flavonoids had no effects on the activity of cystine uptake via xCT. From these results, it has been demonstrated that some flavonoids induce the expression of xCT, resulting in the increase of intracellular glutathione. The common structures of flavonoids which induce xCT seem to be the catechol structure of B ring and the double bond of C ring. These structures may be important to stimulate the Nrf2/Keap 1 system and cause the induction of xCT.

胱氨酸/谷氨酸转运体(XCT)是一种对阴离子形式的胱氨酸和谷氨酸具有高度专一性的阴离子氨基酸的交换媒介。已知这种转运蛋白有助于维持培养中多种哺乳动物细胞内谷胱甘肽的水平。该转运蛋白的活性受到多种刺激的诱导，包括亲电剂、氧化应激、细胞因子和细菌脂多糖。然而，目前还不清楚是否有任何来自食物的物质对XCT和细胞内谷胱甘肽的表达有影响。本研究以黄酮类化合物为研究对象，利用小鼠胰岛细胞系βTC3，寻找对Xct和细胞内谷胱甘肽表达有影响的黄酮类化合物。在这些细胞中，细胞内谷胱甘肽显著增加，以剂量和时间依赖的方式加入槲皮素。除了这种类黄酮，鼠李素、异鼠李素、木犀草素、菲斯汀也有类似的作用。这些黄酮类化合物还诱导XCT介导的半胱氨酸摄取活性。另一方面，山奈酚、杨梅素、栎皮苷、异槲皮苷、桑色素、芹菜素、紫杉酯不能增加β细胞内谷胱甘肽的含量。这些黄酮类化合物对XCT摄取半胱氨酸的活性没有影响。这些结果表明，一些黄酮类化合物诱导XCT的表达，导致细胞内谷胱甘肽的增加。诱导XCT的黄酮类化合物的常见结构似乎是B环的儿茶酚结构和C环的双键。这些结构可能对刺激Nrf2/Keap1系统并导致XCT的诱导起重要作用。

项目成果

Beneficial effect of antioxidants in purified neurons derived from rat cortical culture

• DOI: 10.1016/j.brainres.2006.10.092
• 发表时间: 2007-02
• 期刊: Brain Research
• 影响因子: 2.9
• 作者: J. Sagara;K. Fujiwara;Y. Sakakura;Hideyo Sato;S. Bannai;N. Makino

Redox imbalance in cystine/glutamate transporter-deficient mice

• DOI: 10.1074/jbc.m506439200
• 发表时间: 2005-11-11
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Sato, H;Shiiya, A;Bannai, S
• 通讯作者: Bannai, S

Expression and function of cystine/glutamate transporter in neutrophils

• DOI: 10.1189/jlb.0606385
• 发表时间: 2007-04
• 期刊: Journal of Leukocyte Biology
• 影响因子: 5.5
• 作者: Y. Sakakura;Hideyo Sato;Ayako Shiiya;M. Tamba;J. Sagara;M. Matsuda;N. Okamura;N. Makino;S. Bannai

シスチン・グルタミン酸トランスポーターによるレドックス制御

胱氨酸/谷氨酸转运蛋白的氧化还原调节

• 发表时间: 2006
• 期刊: 医学のあゆみ 別冊
• 作者: Y.Sakakura;et al.;佐藤英世
• 通讯作者: 佐藤英世

Redox regulation by cystine/glutamate transporter.

胱氨酸/谷氨酸转运蛋白的氧化还原调节。

• 发表时间: 2006
• 期刊: Igaku no ayumi
• 作者: Y.Sakakura;et al.;佐藤英世;H.Sato
• 通讯作者: H.Sato