Premium
Protein 4.1R is Involved in the Transport of 5‐Aminolevulinic Acid by Interaction with GATs in MEF Cells
Author(s) -
Ning Shuwei,
Kang Qiaozhen,
Fan Dandan,
Liu Jingjing,
Xue Chaoyue,
Zhang Xiaolin,
Ding Cong,
Zhang Jianying,
Peng Qian,
Ji Zhenyu
Publication year - 2017
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.12842
Subject(s) - chemistry , transporter , cancer cell , microbiology and biotechnology , intracellular , reactive oxygen species , embryonic stem cell , photodynamic therapy , biochemistry , gene , biology , cancer , genetics , organic chemistry
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 m m 5‐ ALA and different concentrations of specific inhibitors of GABA transporters GAT (1‐3). Our results showed that the inhibition of GAT 1 and GAT 2 in particular markedly attenuated the intracellular Pp IX production, reactive oxygen species ( ROS ) level and 5‐ ALA ‐induced photodamage. However, the inhibition of GAT 3 did not show such effects. Further research showed that 4.1R −/− MEF cells had a lower expression of GAT 1 and GAT 2 than 4.1R +/+ MEF cells. Additionally, 4.1R directly bound to GAT 1 and GAT 2. Taken together, GAT 1 and GAT 2 transporters are involved in the uptake of 5‐ ALA in MEF cells. 4.1R plays an important role in transporting 5‐ ALA into cells via at least partly interaction with GAT 1 and GAT 2 transporters in 5‐ ALA ‐ PDT .