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

胱氨酸/谷氨酸转运蛋白（xCT）是阴离子氨基酸的交换媒介，对阴离子形式的胱氨酸和谷氨酸具有高度特异性。这种转运蛋白在培养的多种哺乳动物细胞中有助于维持细胞内谷胱甘肽水平。该转运体的活性可受多种刺激诱导，包括亲电剂、氧化应激、细胞因子和细菌脂多糖。然而，目前尚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，以小鼠胰岛细胞系βTC3细胞为研究对象，寻找对xCT和胞内谷胱甘肽表达有影响的黄酮类化合物。在这些细胞中，细胞内谷胱甘肽通过添加槲皮素以剂量和时间依赖的方式显着增加。除黄酮类外，鼠李素、异鼠李素、木犀草素、非瑟酮也有类似的效果。这些类黄酮还能诱导xCT介导的胱氨酸摄取活性。山奈酚、杨梅素、槲皮素、异槲皮素、桑皮素、芹菜素、杉木素均未增加β tc3细胞内谷胱甘肽的含量。这些类黄酮对通过xCT摄取胱氨酸的活性没有影响。从这些结果可以看出，一些黄酮类化合物可以诱导xCT的表达，从而导致细胞内谷胱甘肽的增加。黄酮类化合物诱导xCT的常见结构似乎是B环的儿茶酚结构和C环的双键结构。这些结构可能对刺激Nrf2/Keap 1系统和诱导xCT很重要。

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.