Cholesterol-Depletion-Induced Membrane Repair Carries a Raft Conformer of P-Glycoprotein to the Cell Surface, Indicating Enhanced Cholesterol Trafficking in MDR Cells, Which Makes Them Resistant to Cholesterol Modifications
Abstract
:1. Introduction
2. Results
2.1. Cholesterol Extraction Increased the Amount of Raft-Associated, UIC2-Binding Conformer of P-gp in Cell Surface Membranes
2.2. Cholesterol Depletion-Induced Rise in the UIC2-Binding P-gp Conformer Is the Result of Increased Exocytosis and Not Decreased Endocytosis
2.3. Inhibition of Exocytosis Prevents the Increase in UIC2-Bound P-gp Caused by Cholesterol Depletion
2.4. UIC2-Binding P-gp Represents the Cholesterol-Dependent Trafficking of Rafts
2.5. Exocytosis of LAMP1 and LAMP2 Was Enhanced after Cyclodextrin Treatment in a Calcium and Cholesterol-Dependent Manner
2.6. Enhanced Number and Increased Stability of Lysosomes in 3T3-MDR1 Cells
2.7. Lysosomes of 3T3-MDR1 Cells Were More Resistant to Photolysis Than Lysosomes of Parental NIH-3T3 Cells, even after Cholesterol Depletion
2.8. The More Effective Repair Mechanisms of 3T3-MDR1 Cells Result in Higher Viability after Cholesterol Modulation
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Chemicals, Antibodies
4.3. Kd and Bmax Values of Antibodies, Cell Membrane Cholesterol Modulations
4.4. Endocytosis Measurements
4.5. Exocytosis of the UIC2 Reactive Fraction
4.6. Inhibition of Exocytosis
4.7. Cell Surface Appearance of LAMP1 and LAMP2 after Cholesterol Extraction
4.8. Measurement of Cellular Cholesterol Levels and Cell Viability of MDR1 Transfected and Non-Transfected Cell Lines
4.9. Determination of Lysosome Content of Cells
4.10. Measurements of Photo-Destruction of Lysosomes
4.11. Analysis of Image Series
4.12. Cholesterol Extraction Effect on Lysosomotropic Dye Accumulation
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gutay-Tóth, Z.; Gellen, G.; Doan, M.; Eliason, J.F.; Vincze, J.; Szente, L.; Fenyvesi, F.; Goda, K.; Vecsernyés, M.; Szabó, G.; et al. Cholesterol-Depletion-Induced Membrane Repair Carries a Raft Conformer of P-Glycoprotein to the Cell Surface, Indicating Enhanced Cholesterol Trafficking in MDR Cells, Which Makes Them Resistant to Cholesterol Modifications. Int. J. Mol. Sci. 2023, 24, 12335. https://doi.org/10.3390/ijms241512335
Gutay-Tóth Z, Gellen G, Doan M, Eliason JF, Vincze J, Szente L, Fenyvesi F, Goda K, Vecsernyés M, Szabó G, et al. Cholesterol-Depletion-Induced Membrane Repair Carries a Raft Conformer of P-Glycoprotein to the Cell Surface, Indicating Enhanced Cholesterol Trafficking in MDR Cells, Which Makes Them Resistant to Cholesterol Modifications. International Journal of Molecular Sciences. 2023; 24(15):12335. https://doi.org/10.3390/ijms241512335
Chicago/Turabian StyleGutay-Tóth, Zsuzsanna, Gabriella Gellen, Minh Doan, James F. Eliason, János Vincze, Lajos Szente, Ferenc Fenyvesi, Katalin Goda, Miklós Vecsernyés, Gábor Szabó, and et al. 2023. "Cholesterol-Depletion-Induced Membrane Repair Carries a Raft Conformer of P-Glycoprotein to the Cell Surface, Indicating Enhanced Cholesterol Trafficking in MDR Cells, Which Makes Them Resistant to Cholesterol Modifications" International Journal of Molecular Sciences 24, no. 15: 12335. https://doi.org/10.3390/ijms241512335
APA StyleGutay-Tóth, Z., Gellen, G., Doan, M., Eliason, J. F., Vincze, J., Szente, L., Fenyvesi, F., Goda, K., Vecsernyés, M., Szabó, G., & Bacso, Z. (2023). Cholesterol-Depletion-Induced Membrane Repair Carries a Raft Conformer of P-Glycoprotein to the Cell Surface, Indicating Enhanced Cholesterol Trafficking in MDR Cells, Which Makes Them Resistant to Cholesterol Modifications. International Journal of Molecular Sciences, 24(15), 12335. https://doi.org/10.3390/ijms241512335