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（Cystine/glutamate transporter，xCT）是一种阴离子氨基酸交换剂，对胱氨酸和谷氨酸的阴离子形式具有高度特异性。已知这种转运蛋白有助于维持培养物中许多类型哺乳动物细胞的细胞内谷胱甘肽水平。该转运蛋白的活性由各种刺激物诱导，包括亲电试剂、氧化应激、细胞因子和细菌脂多糖。然而，目前尚不清楚任何来源于食物的材料是否对xCT和细胞内谷胱甘肽的表达有影响。在本研究中，我们专注于黄酮类化合物，并使用小鼠胰岛细胞系β TC 3细胞寻找对xCT和细胞内谷胱甘肽表达有影响的各种黄酮类化合物。在这些细胞中，细胞内的谷胱甘肽显着增加，除了槲皮素的剂量和时间依赖性的方式。除此之外，鼠李素、异鼠李素、木犀草素、非瑟酮也表现出类似的作用。这些黄酮类化合物还诱导由xCT介导的胱氨酸摄取活性。山奈酚、杨梅素、槲皮苷、异槲皮苷、桑色素、芹菜素、紫杉叶素对β TC 3细胞内谷胱甘肽含量无明显影响。这些黄酮类化合物通过xCT对胱氨酸摄取的活性没有影响。从这些结果中，已经证明，一些类黄酮诱导xCT的表达，导致细胞内谷胱甘肽的增加。诱导xCT的黄酮类化合物的共同结构可能是B环的邻苯二酚结构和C环的双键。这些结构对于刺激Nrf 2/Keap 1系统并引起xCT的诱导可能是重要的。

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.