Expression of the activity of cystine/glutamate exchange transporter, system x_c⁻, by xCT and rBAT

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• 作者：Wang ; Hongyu ; Tamba ; Michiko ; Kimata ; Mayumi ; Sakamoto ; Kazuichi ; Bannai ; Shiro ; Sato ; Hideyo
• 关键词：Cystine ; System x_c^&minus ; ; rBAT ; 4F2 heavy chain ; Amino acid transporter ; Heterodimer
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2003
• 出版时间：June 6, 2003
• 年：2003
• 卷：305
• 期：3
• 页码：611-618
• 全文大小：233 K

文摘

The expression of the activity of cystine/glutamate exchange transporter, designated system x_c⁻, requires two components, xCT and 4F2 heavy chain (4F2hc) in Xenopus oocytes. rBAT (related to b^0,+ amino acid transporter) has a significant homology to 4F2hc and is known to be located in the apical membrane of epithelial cells. To determine whether xCT can associate with rBAT and express the activity of system x_c⁻, xCT, and rBAT were co-expressed in Xenopus oocytes and in mammalian cultured cells. In the oocytes injected with rBAT cRNA alone, the activities of cystine and arginine transport were induced, indicating that the system b^0,+-like transporter was expressed by associating the exogenous rBAT with an endogenous b^0,+AT-like factor as reported previously. In the oocytes injected with xCT and rBAT cRNAs, the activity of cystine transport was further induced. This induced activity of cystine transport was partially inhibited by glutamate or arginine and completely inhibited by adding both amino acids. In these oocytes, the activity of glutamate transport was also induced and it was strongly inhibited by cystine. In NIH3T3 cells transfected with xCT cDNA alone, the activity of cystine transport was significantly increased, and in the cells transfected with both xCT and rBAT cDNAs, the activity of cystine transport was further enhanced. The enhanced activity was Na⁺-independent and was inhibited by glutamate and homocysteate. These results indicate that rBAT can replace 4F2hc in the expression of the activity of system x_c⁻ and suggest that system x_c⁻ activity could be expressed in the apical membrane of epithelial cells.