Transport of glutathione conjugates into secretory vesicles is mediated by the multidrug-resistance protein 1
✍ Scribed by Marja J. A. Van Luyn; Michael Müller; Johan Renes; Coby Meijer; Rick J. Scheper; Edith F. Nienhuis; Nanno H. Mulder; Peter L. M. Jansen; Elisabeth G. E. De Vries
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 451 KB
- Volume
- 76
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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.