The effect of radixin knockdown on the expression and efflux function of MRP2 in SGC-7901 cells

详细信息	查看全文 | 推荐本文 |

• 作者：Xiao-Jie He^a ; ^{09210700099@fudan.edu.cn} ; Wei-Rong Wang^a ; ^{wrwang@fudan.edu.cn} ; Yun Zhang^b ; ^{yunzhang15@sina.com} ; Qing Yang^a ; ^{yangqing68@fudan.edu.cn}
• 关键词：ERM ; MRP2 ; Expression ; Function ; Regulation
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2012
• 期刊代码：15_09280987
• 类别：pha
• 出版时间：15 August, 2012
• 卷：46
• 期：5
• 页码：426-434
• 文件大小：780 K

摘要

Multidrug resistance-associated protein 2 (MRP2, ABCC2) is the second member of the MRP transporter family and functions physiologically as an organic anion transporter. Earlier studies have confirmed that radixin, which is a member of the ERM (ezrin/radixin/moesin) family, modulates MRP2 localization at the canalicular membrane in hepatocytes. The relationship between radixin and MRP2 - particularly, the effect of radixin on the expression and function of MRP2 in cells or tissues that co-express all three ERM proteins - has not been well studied. To examine the role of radixin in the expression and function of MRP2 and other MRPs, we chose human gastric carcinoma SGC-7901 cells that express all three ERM proteins rather than hepatocytes, which predominantly express radixin. Radixin stable knockdown SGC-7901 cells, which were constructed by RNAi, exhibited no compensatory up-regulation of ezrin or moesin. The mRNA expression profiles of MRPs in the radixin knockdown cells were primarily evaluated by RT-PCR. Real time quantitative RT-PCR and western blot analysis revealed that the radixin deficiency caused the mRNA and protein expression levels of MRP2 to be reduced by about 50%, respectively. Accordingly, efflux and MTT assays showed that the radixin knockdown cells exhibited lower efflux ability with respect to calcein but no significant change in cell viability. In conclusion, among the MRP1-6 family members, radixin selectively modulates the expression and function of MRP2 in a system co-expressing all three ERM proteins.