ArticleProceedings of the National Academy of Sciences of the United States of America2002
The multidrug transporter, P-glycoprotein, actively mediates cholesterol redistribution in the cell membrane.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.
- ABCB1 C3435T polymorphism and the lipid-lowering response in hypercholesterolemic patients on statins: a meta-analysis.Lipids in health and disease · 2015Pooled it
- Mapping the inhibition landscape of P-glycoprotein via conformational ensemble docking.Scientific reports · 2026Article
- Elucidating the Complex Structural and Molecular Mechanisms Driving P-Glycoprotein-Mediated Transport of Cardiac Glycosides.International journal of molecular sciences · 2025Article
- Beyond ADME: The Endogenous Functions of Drug Transporters and Its Impact on Human Disease.Pharmaceutics · 2025Review
- Designing novel cabozantinib analogues as p-glycoprotein inhibitors to target cancer cell resistance using molecular docking study, ADMET screening, bioisosteric approach, and molecular dynamics simulations.Frontiers in chemistry · 2025Article
- Nucleotide asymmetry and flexible linker dynamics modulate drug efflux cycle of P-glycoprotein, A computational study.Computational and structural biotechnology journal · 2025Article
- Mechanistic insights into P-glycoprotein ligand transport and inhibition revealed by enhanced molecular dynamics simulations.Computational and structural biotechnology journal · 2024Article
- Experimental and Computational Methods to Assess Central Nervous System Penetration of Small Molecules.Molecules (Basel, Switzerland) · 2024Review
- Drug-Induced Conformational Dynamics of P-Glycoprotein Underlies the Transport of Camptothecin Analogs.International journal of molecular sciences · 2023Article
- 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 · 2023Article
- SIAH1 ubiquitination-modified HMGCR inhibits lung cancer progression and promotes drug sensitivity through cholesterol synthesis.Cancer cell international · 2023Article
- Drug Resistance in Medulloblastoma Is Driven by YB-1, ABCB1 and a Seven-Gene Drug Signature.Cancers · 2023Article
- PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Clinical Significance of Lipid Transport Function of ABC Transporters in the Innate Immune System.Membranes · 2022Review
- The Importance of the Plasma Membrane in Atherogenesis.Membranes · 2022Review
- NLRP3 Inflammasome Priming and Activation Are Regulated by a Phosphatidylinositol-Dependent Mechanism.ImmunoHorizons · 2022Article
- Pharmaceutical Formulations with P-Glycoprotein Inhibitory Effect as Promising Approaches for Enhancing Oral Drug Absorption and Bioavailability.Pharmaceutics · 2021Review
- The Role of ABC Transporters in Lipid Metabolism and the Comorbid Course of Chronic Obstructive Pulmonary Disease and Atherosclerosis.International journal of molecular sciences · 2021Review
- The bidirectional relationship between CFTR and lipids.Communications biology · 2020Review
- Probing cholesterol binding and translocation in P-glycoprotein.Biochimica et biophysica acta. Biomembranes · 2020Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P-glycoprotein (P-gp) is a plasma membrane ATP-binding cassette transporter, responsible for multidrug resistance in tumor cells. P-gp catalyzes the ATP hydrolysis-dependent efflux of numerous amphiphilic compounds of unrelated chemical structures. In the absence of any identified substrate, P-gp exhibits an apparently futile, basal ATPase activity. By using native membrane vesicles containing high amounts of P-gp, we show here that (i) this basal ATPase activity is tightly dependent on the presence of cholesterol in the membrane; (ii) the stimulation of P-gp ATPase activity by drugs transported by P-gp is higher in the absence than in the presence of cholesterol and, conversely, the stimulation of P-gp ATPase activity by cholesterol is higher in the absence than in the presence of known P-gp substrates; (iii) P-gp mediates the ATP-dependent relocation of cholesterol from the cytosolic leaflet to the exoplasmic leaflet of the plasma membrane; and (iv) the decrease of the cholesterol dependence of P-gp ATPase activity induced by known P-gp substrates is correlated with the inhibition of the ATP-dependent cholesterol redistribution within the membrane. These data are highly evocative of a coupling between the basal ATPase activity of P-gp and its intramembrane cholesterol-redistribution function, and they are fully consistent with the possibility that P-gp may actively translocate cholesterol in the membrane. Finally, this P-gp-mediated cholesterol redistribution in the cell membrane makes it likely that P-gp contributes in stabilizing the cholesterol-rich microdomains, rafts and caveolae, and that it is involved in the regulation of cholesterol trafficking in cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.