Transport of glutathione conjugates into secretory vesicles is mediated by the multidrug-resistance protein 1

M. J. van Luyn; M. Müller; J. Renes; C. Meijer; R. J. Scheper; E. F. Nienhuis; N. H. Mulder; P. L. Jansen; E. G. de Vries

doi:10.1002/(SICI)1097-0215(19980330)76:1

Transport of glutathione conjugates into secretory vesicles is mediated by the multidrug-resistance protein 1

M. J. van Luyn, M. Müller, J. Renes, C. Meijer, R. J. Scheper, E. F. Nienhuis, N. H. Mulder, P. L. Jansen, E. G. de Vries

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Abstract

Intracellular glutathione-conjugate transport was evaluated in the human small cell lung carcinoma cell line GLC4 with low multidrug resistance protein (MRP1) expression and its 300x doxorubicin-resistant, MRP1-over-expressing, GLC4-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 GLC4-Adr. Immunotransmission electron microscopy showed that MRP1 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 GLC4-Adr cells, doxorubicin also was transported in vesicles, with an arrest in vesicle release from the Golgi complex. Our results indicate that MRP1 functions as a glutathione-conjugate transporter not only at the plasma membrane but also in intracellular secretory vesicles

Original language	English
Pages (from-to)	55-62
Journal	International journal of cancer. Journal international du cancer
Volume	76
Issue number	1
DOIs	https://doi.org/10.1002/(SICI)1097-0215(19980330)76:1
Publication status	Published - 1998

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10.1002/(SICI)1097-0215(19980330)76:1

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van Luyn, M. J., Müller, M., Renes, J., Meijer, C., Scheper, R. J., Nienhuis, E. F., Mulder, N. H., Jansen, P. L., & de Vries, E. G. (1998). Transport of glutathione conjugates into secretory vesicles is mediated by the multidrug-resistance protein 1. International journal of cancer. Journal international du cancer, 76(1), 55-62. https://doi.org/10.1002/(SICI)1097-0215(19980330)76:1

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title = "Transport of glutathione conjugates into secretory vesicles is mediated by the multidrug-resistance protein 1",

abstract = "Intracellular glutathione-conjugate transport was evaluated in the human small cell lung carcinoma cell line GLC4 with low multidrug resistance protein (MRP1) expression and its 300x doxorubicin-resistant, MRP1-over-expressing, GLC4-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 GLC4-Adr. Immunotransmission electron microscopy showed that MRP1 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 GLC4-Adr cells, doxorubicin also was transported in vesicles, with an arrest in vesicle release from the Golgi complex. Our results indicate that MRP1 functions as a glutathione-conjugate transporter not only at the plasma membrane but also in intracellular secretory vesicles",

author = "{van Luyn}, {M. J.} and M. M{\"u}ller and J. Renes and C. Meijer and Scheper, {R. J.} and Nienhuis, {E. F.} and Mulder, {N. H.} and Jansen, {P. L.} and {de Vries}, {E. G.}",

year = "1998",

doi = "10.1002/(SICI)1097-0215(19980330)76:1",

language = "English",

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journal = "International journal of cancer. Journal international du cancer",

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van Luyn, MJ, Müller, M, Renes, J, Meijer, C, Scheper, RJ, Nienhuis, EF, Mulder, NH, Jansen, PL & de Vries, EG 1998, 'Transport of glutathione conjugates into secretory vesicles is mediated by the multidrug-resistance protein 1', International journal of cancer. Journal international du cancer, vol. 76, no. 1, pp. 55-62. https://doi.org/10.1002/(SICI)1097-0215(19980330)76:1

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AU - van Luyn, M. J.

AU - Müller, M.

AU - Renes, J.

AU - Meijer, C.

AU - Scheper, R. J.

AU - Nienhuis, E. F.

AU - Mulder, N. H.

AU - Jansen, P. L.

AU - de Vries, E. G.

PY - 1998

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N2 - Intracellular glutathione-conjugate transport was evaluated in the human small cell lung carcinoma cell line GLC4 with low multidrug resistance protein (MRP1) expression and its 300x doxorubicin-resistant, MRP1-over-expressing, GLC4-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 GLC4-Adr. Immunotransmission electron microscopy showed that MRP1 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 GLC4-Adr cells, doxorubicin also was transported in vesicles, with an arrest in vesicle release from the Golgi complex. Our results indicate that MRP1 functions as a glutathione-conjugate transporter not only at the plasma membrane but also in intracellular secretory vesicles

AB - Intracellular glutathione-conjugate transport was evaluated in the human small cell lung carcinoma cell line GLC4 with low multidrug resistance protein (MRP1) expression and its 300x doxorubicin-resistant, MRP1-over-expressing, GLC4-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 GLC4-Adr. Immunotransmission electron microscopy showed that MRP1 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 GLC4-Adr cells, doxorubicin also was transported in vesicles, with an arrest in vesicle release from the Golgi complex. Our results indicate that MRP1 functions as a glutathione-conjugate transporter not only at the plasma membrane but also in intracellular secretory vesicles

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