Resveratrol Protects Membranes from PLA1 and PLA2 Hydrolytic Attack

Abstract

Background: Resveratrol is a polyphenol found in red wine. In this work we tested the hypothesis that resveratrol protects membranes from the hydrolytic attack of phospholipase A1, PLA1, and phospholipase A2, PLA2, which hydrolyze the sn-1 and sn-2 ester bonds of phospholipids, respectively, producing a fatty acid and a lysolipid. Methods: Molecular dynamics simulation studies were used to study the location of resveratrol within dipalmitoyl-phosphatidylcholine, DPPC, membranes at 37°C. Also liposomes were prepared with DPPC, and Distearoyl-phosphatidylcholine, DSPC, having 0, 5, 9 and 33 mole % resveratrol and were challenged for 10 minutes by the presence of PLA1, or PLA2. The resulting free fatty acid, FFA, from the PLA1 and PLA2 challenge was measured using the ADIFAB and ADIFAB2 kits, respectively. Results: Computational studies show that resveratrol decreases the bilayer thickness and increases the membrane surface area. Also resveratrol has high probability to form hydrogen bonds with sn-1 and sn-2 ester groups. When DPPC and DSPC membranes were challenged with PLA2, there was significantly less FFA in the presence of all of the concentrations of resveratrol compared to the control. This result signifies the fact that all resveratrol concentrations were able to protect the DPPC and DSPC membranes from the PLA2 challenge. Furthermore, all the concentrations of resveratrol tested protected DSPC from PLA1 challenge, whereas 5 and 9 and not the 33 molar% resveratrol protected DPPC from the PLA1 hydrolytic attack challenge. Conclusion: In conclusion, resveratrol assumes a protective position in the part of head group of the phospholipids bilayers proximal to fatty acyl chains and is able to protect the phospholipids from the hydrolytic attack of the PLAs.