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

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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.