Related Experiment Video
Updated: Jul 4, 2026
11:07
Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
P-glycoprotein inhibition by membrane cholesterol modulation
Ferenc Fenyvesi1, Eva Fenyvesi, Lajos Szente
1Department of Pharmaceutical Technology, University of Debrecen, PO Box 78, 4010 Debrecen, Hungary. fenyvesi@king.pharmacol.dote.hu
Summary
Modulating membrane cholesterol with cyclodextrins affects P-glycoprotein (Pgp) function by altering its lipid microenvironment. This study shows Pgp inhibition is linked to membrane structure changes, not cytotoxicity.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- P-glycoprotein (Pgp) mediates multidrug resistance by exporting chemotherapeutics.
- Pgp function is sensitive to membrane cholesterol and raft localization.
Purpose of the Study:
- Investigate how altering membrane cholesterol affects Pgp function and localization.
- Determine if Pgp inhibition by cyclodextrins is due to microenvironment changes or cytotoxicity.
Main Methods:
- Modulated membrane cholesterol using DIMEB and Chol-DIMEB.
- Assessed Pgp function via calcein accumulation.
- Measured membrane lipid packing with MC540 staining.
Main Results:
- Cholesterol modulation altered lipid packing and Pgp raft association.
- Cyclodextrin treatments increased cell membrane permeability but not ATP levels.
- Pgp function was inhibited following cholesterol modulation.
Conclusions:
- Pgp inhibition by cyclodextrins results from changes in its membrane microenvironment.
- The observed effects are not due to general cytotoxicity or ATP depletion.
Related Concept Videos
01:29Cholesterol: Significance and Regulation
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...
01:23Inhibitors of Gram-positive Cell Wall Synthesis
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
01:30Inhibitors of Viral Protein Synthesis
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
01:12GPCR Desensitization
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
01:29GPI Anchoring of Proteins in the ER Membrane
GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...