3 years ago

Protein 4.1R is Involved in the Transport of 5-Aminolevulinic Acid by Interaction with GATs in MEF Cells

Xiaolin Zhang, Dandan Fan, Chaoyue Xue, Jingjing Liu, Qiaozhen Kang, Shuwei Ning, Qian Peng, Zhenyu Ji, Cong Ding, Jianying Zhang
5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT) has been successfully used in the treatment of cancers. However, the mechanism of 5-ALA transportation into cancer cells is still not fully elucidated. Previous studies have confirmed that the efficiency of 5-ALA-PDT could be affected by the membrane skeleton protein 4.1R. In this study we investigated the role of 4.1R in the transport of 5-ALA into cells. Wild-type (4.1R+/+) and 4.1R gene knockout (4.1R-/-) mouse embryonic fibroblast (MEF) cells were incubated with 1 mM 5-ALA and different concentrations of specific inhibitors of GABA transporters GAT(1-3). Our results showed that the inhibition of GAT1 and GAT2 in particular markedly attenuated the intracellular PpIX production, reactive oxygen species (ROS) level and 5-ALA-induced photodamage. However, the inhibition of GAT3 did not show such effects. Further research showed that 4.1R-/- MEF cells had a lower expression of GAT1 and GAT2 than 4.1R+/+ MEF cells. Additionally, 4.1R directly bound to GAT1 and GAT2. Taken together, GAT1 and GAT2 transporters are involved in the uptake of 5-ALA by the MEF cells. 4.1R plays an important role in transporting 5-ALA into cells via at least partly interaction with GAT1 and GAT2 transporters in 5-ALA-PDT. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/php.12842

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