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Transport of glutathione conjugates into secretory vesicles is mediated by the multidrug‐resistance protein 1
Author(s) -
Van Luyn Marja J. A.,
Müller Michael,
Renes Johan,
Meijer Coby,
Scheper Rick J.,
Nienhuis Edith F.,
Mulder Nanno H.,
Jansen Peter L. M.,
De Vries Elisabeth G. E.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980330)76:1<55::aid-ijc10>3.0.co;2-f
Subject(s) - vesicle , brefeldin a , glutathione , intracellular , golgi apparatus , microbiology and biotechnology , vesicular transport protein , biology , biochemistry , conjugate , multiple drug resistance , chemistry , biophysics , membrane , cell , mathematical analysis , enzyme , mathematics , antibiotics
Intracellular glutathione‐conjugate transport was evaluated in the human small cell lung carcinoma cell line GLC 4 with low multidrug resistance protein (MRP 1 ) expression and its 300× doxorubicin‐resistant, MRP 1 ‐over‐expressing, GLC 4 ‐Adr subline. Transport of non‐toxic concentrations of monochlorobimane and 5‐chloro‐methyl fluorescein diacetate was evaluated using fluorescence microscopy. After exposure to these compounds, fluorescence was observed especially in intracellular vesicles in GLC 4 ‐Adr. Immunotransmission electron microscopy showed that MRP 1 was present in the vesicle membranes and plasma membrane, while inside the vesicles the glutathione conjugate of 1‐chloro‐2,4‐dinitrobenzene could be detected. Experiments with brefeldin A, which induces arrest in vesicle release from the Golgi complex, indicated that these vesicles may originate from the trans‐Golgi network. In GLC 4 ‐Adr cells, doxorubicin also was transported in vesicles, with an arrest in vesicle release from the Golgi complex. Our results indicate that MRP 1 functions as a glutathione‐conjugate transporter not only at the plasma membrane but also in intracellular secretory vesicles. Int. J. Cancer 76:55–62, 1998.© 1998 Wiley‐Liss, Inc.