ArticleThe Journal of biological chemistry2010
The anti-inflammatory drug indomethacin alters nanoclustering in synthetic and cell plasma membranes.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 50 citations in OpenAlex.
- Lipid Raft Membrane Interactivity Correlating with Cyclooxygenase-2 Selectivity of Non-Steroidal Anti-Inflammatory Drugs.Membranes · 2025Article
- Topological Heterogeneity of Protein Kinase C Modulators in Human T-Cells Resolved with In-Cell Dynamic Nuclear Polarization NMR Spectroscopy.Journal of the American Chemical Society · 2024Article
- A Biomimetic Multiparametric Assay to Characterise Anti-Amyloid Drugs.International journal of molecular sciences · 2023Article
- Spin-Labeled Diclofenac: Synthesis and Interaction with Lipid Membranes.Molecules (Basel, Switzerland) · 2023Article
- RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling.FEBS letters · 2023Review
- Assessment of Pharmacological Potential of Novel Exopolysaccharide Isolated from MarineLife (Basel, Switzerland) · 2022Article
- Dioctadecyldimethylammonium bromide, a surfactant model for the cell membrane: Importance of microscopic dynamics.Structural dynamics (Melville, N.Y.) · 2020Review
- Growth inhibitory effects of PC-NSAIDs on human breast cancer subtypes in cell culture.Oncology letters · 2019Article
- The Lipid Bilayer Provides a Site for Cortisone Crystallization at High Cortisone Concentrations.Scientific reports · 2016Article
- Usefulness of targeting lymphocyte Kv1.3-channels in the treatment of respiratory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2015Article
- Trace membrane additives affect lipid phases with distinct mechanisms: a modified Ising model.European biophysics journal : EBJ · 2015Article
- Caveolae regulate the nanoscale organization of the plasma membrane to remotely control Ras signaling.The Journal of cell biology · 2014Article
- Liquid general anesthetics lower critical temperatures in plasma membrane vesicles.Biophysical journal · 2013Article
- Bile acids modulate signaling by functional perturbation of plasma membrane domains.The Journal of biological chemistry · 2013Article
- Advent of novel phosphatidylcholine-associated nonsteroidal anti-inflammatory drugs with improved gastrointestinal safety.Gut and liver · 2013Article
- Fendiline inhibits K-Ras plasma membrane localization and blocks K-Ras signal transmission.Molecular and cellular biology · 2013Article
- Insight into NSAID-induced membrane alterations, pathogenesis and therapeutics: characterization of interaction of NSAIDs with phosphatidylcholine.Biochimica et biophysica acta · 2012Article
- Nonsteroidal anti-inflammatory drugs alter the spatiotemporal organization of Ras proteins on the plasma membrane.The Journal of biological chemistry · 2012Article
- Ras trafficking, localization and compartmentalized signalling.Seminars in cell & developmental biology · 2012Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The nonsteroidal anti-inflammatory drug indomethacin exhibits diverse biological effects, many of which have no clear molecular mechanism. Membrane-bound receptors and enzymes are sensitive to their phospholipid microenvironment. Amphipathic indomethacin could therefore potentially modulate cell signaling by changing membrane properties. Here we examined the effect of indomethacin on membrane lateral heterogeneity. Fluorescence lifetime imaging of cells expressing lipid-anchored probes revealed that treatment of BHK cells with therapeutic levels of indomethacin enhances cholesterol-dependent nanoclustering, but not cholesterol-independent nanoclustering. Immuno-electron microscopy and quantitative spatial mapping of intact plasma membrane sheets similarly showed a selective effect of indomethacin on promoting cholesterol-dependent, but not cholesterol-independent, nanoclustering. To further evaluate the biophysical effects of indomethacin, we measured fluorescence polarization of the phase-sensitive probe Laurdan and FRET between phase-partitioning probes in model bilayers. Therapeutic levels of indomethacin enhanced phase separation in DPPC/DOPC/Chol (1:1:1) and DPPC/Chol membranes in a temperature-dependent manner, but had minimal effect on the phase behavior of pure DOPC at any temperature. Taken together, the imaging results on intact epithelial cells and the biophysical assays of model membranes suggest that indomethacin can enhance phase separation and stabilize cholesterol-dependent nanoclusters in biological membranes. These effects on membrane lateral heterogeneity may have significant consequences for cell signaling cascades that are assembled on the plasma membrane.
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