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ID 51552
フルテキストURL
著者
Kobuchi, Hirotsugu Okayama Univ, Dept Cell Chem, Grad Sch Med Dent & Pharmaceut Sci
Moriya, Koko Yamaguchi Univ, Grad Sch Med
Ogino, Tetsuya Okayama Prefectural Univ, Dept Nursing Sci, Fac Hlth & Welf Sci
Fujita, Hirofumi Okayama Univ, Dept Cytol & Histol, Grad Sch Med Dent & Pharmaceut Sci Kaken ID researchmap
Inoue, Keiji Kochi Med Sch, Dept Urol
Shuin, Taro Kochi Med Sch, Dept Urol
Yasuda, Tatsuji Okayama Univ, Dept Cell Chem, Grad Sch Med Dent & Pharmaceut Sci
Utsumi, Kozo Okayama Univ, Dept Cytol & Histol, Grad Sch Med Dent & Pharmaceut Sci
Utsumi, Toshihiko Yamaguchi Univ, Grad Sch Med
抄録
Accumulation of protoporphyrin IX (PpIX) in malignant cells is the basis of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy. We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. Among these proteins, only ABCG2 correlated negatively with ALA-mediated PpIX accumulation. Both a subcellular fractionation study and confocal laser microscopic analysis revealed that ABCG2 was distributed not only in the plasma membrane but also intracellular organelles, including mitochondria. In addition, mitochondrial ABCG2 regulated the content of ALA-mediated PpIX in mitochondria, and Ko143, a specific inhibitor of ABCG2, enhanced mitochondrial PpIX accumulation. To clarify the possible roles of mitochondrial ABCG2, we characterized stably transfected-HEK (ST-HEK) cells overexpressing ABCG2. In these ST-HEK cells, functionally active ABCG2 was detected in mitochondria, and treatment with Ko143 increased ALA-mediated mitochondrial PpIX accumulation. Moreover, the mitochondria isolated from ST-HEK cells exported doxorubicin probably through ABCG2, because the export of doxorubicin was inhibited by Ko143. The susceptibility of ABCG2 distributed in mitochondria to proteinase K, endoglycosidase H and peptide-N-glycosidase F suggested that ABCG2 in mitochondrial fraction is modified by N-glycans and trafficked through the endoplasmic reticulum and Golgi apparatus and finally localizes within the mitochondria. Thus, it was found that ABCG2 distributed in mitochondria is a functional transporter and that the mitochondrial ABCG2 regulates ALA-mediated PpIX level through PpIX export from mitochondria to the cytosol.
発行日
2012-11-26
出版物タイトル
PLoS ONE
7巻
11号
出版者
Public Library Science
ISSN
1932-6203
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1371/journal.pone.0050082
言語
English
著作権者
© 2012 Kobuchi et al.
論文のバージョン
publisher
査読
有り
DOI
Web of Science KeyUT