Study of protective effect of Resveratrol on the mitochondrial membrane integrity upon interaction with oligomeric intermediates of Hen Egg White Lysozyme

Recent findings demonstrate that oligomeric species, as toxic intermediates during the formation of mature fibrils, by increasing membrane permeability leading to cell death. Among these, the membrane of interest is mitochondria, so that mitochondrial dysfunction is a common feature of many disorders relating to protein aggregation. Therefore, in the present study interaction of the original native structure, oligomeric intermediates and amyloid fibrils of hen egg white lysozyme (HEWL) with mitochondrial membranes (as an in vitro biological model) were investigated. First structural characteristics of prefibrillar intermediates have been investigated using a range of techniques including fluorescence (ThT and ANS) and circular dichroism, and possible mitochondrial membrane permeabilization was determined following release of marker enzymes. Results presented demonstrate release of mitochondrial enzymes upon exposure to HEWL oligomers, whereas native monomer or mature fibrils were totally ineffective. It seems that increased surface hydrophobicity of HEWL oligomers enhanced their capacity to interact with mitochondrial membranes. Then we investigated the ability of Resveratrol to counteract mitochondrial membrane permeabilization induced by HEWL oligomers. The results demonstrate that Resveratrol can effectively hinder oligomer-mediated mitochondrial permeabilization. It has been suggests that Resveratrol via its membrane stabilizing effects protects mitochondria against oligomer toxicity. These may serve for design of novel therapeutic agents against disorders relating to protein misfolding and aggregation