Membrane Approach to Understand the Pleiotropic Effects of Resveratrol
Resveratrol is a natural polyphenol compound with great potential in the cancer therapy, cardiovascular protection, and neurodegenerative disorders. The mechanism of action of resveratrol may be associated to its capacity of modulating cell membrane structure and function, thereby influencing the activity of several membrane associating receptors, proteins and enzymes.
The present research reveals potential molecular interactions between resveratrol and lipid rafts found in cell membranes, bringing a new membrane approach to understand the pleiotropic effects of this phytochemical.
Förster resonance energy transfer (FRET), DPH fluorescence quenching by TEMPO, and Triton X-100 detergent resistance assay have been employed to monitor lipid phase separation in model membranes. Unilamellar liposomes composed of phosphatidylcholine, cholesterol and sphingomyelin were chosen as membrane mimetic systems.
The results indicate that resveratrol is able to incorporate in lipid bilayers, inducing phase separation, stabilizing and promoting the formation of ordered domains (lipid rafts) that can act as organizing centers for the assembly of proteins and receptors, which in turn may be involved in the cell signaling and cellular processes.
In conclusion, the influence of resveratrol on the regulation of lipid domains formation and stability provide a rational approach to better understand the therapeutic effects of this promising compound.
Neves AR1, Nunes C1, Reis S2.[expand title=”Show Affiliations”]
- UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
- UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. Electronic address: [email protected] [/expand]
Resveratrol is a polyphenol compound with great value in cancer therapy, cardiovascular protection, and neurodegenerative disorders. The mechanism by which resveratrol exerts such pleiotropic effects is not yet clear and there is a huge need to understand the influence of this compound on the regulation of lipid domains formation on membrane structure.
The aim of the present study was to reveal potential molecular interactions between resveratrol and lipid rafts found in cell membranes by means of Förster resonance energy transfer, DPH fluorescence quenching, and triton X-100 detergent resistance assay. Liposomes composed of egg phosphatidylcholine, cholesterol, and sphingomyelin were used as model membranes.
The results revealed that resveratrol induces phase separation and formation of liquid-ordered domains in bilayer structures. The formation of such tightly packed lipid rafts is important for different signal transduction pathways, through the regulation of membrane-associating proteins, that can justify several pharmacological activities of this compound.
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