THE DIETARY ANTIOXIDANT RESVERATROL AFFECTS REDOX CHANGES OF PPARΑ ACTIVITY

Gene-environment interaction is behind the pathogenesis of most widespread diseases, and nutrition is among the environmental factors with the highest impact on human health. The mechanisms involved in the interaction between nutritional factors and the genetic background of individuals are still unclear. The aim of this study was to investigate whether resveratrol (RES), an antioxidant polyphenol of red wine, can influence the activity of PPARalpha in the rat hepatoma cell line McArdle-RH7777. PPARalpha is a transcriptional factor that regulates gene expression when activated by endogenous or exogenous long-chain fatty acids. Its activation results in significant protection from cardiovascular diseases in humans. METHODS AND RESULTS: By means of the electromobility shift assay (EMSA), we observed that PPARalpha is redox-sensitive as it displays reduced DNA-binding activity following in vivo treatment of the cells with 1mmol/L diethylmaleate (DEM), a glutathione-depleting agent. This finding could be relevant considering the important role of redox balance in pathological and physiological processes. We also observed a dual effect of 100mumol/L RES on PPARalpha activity: it was able to prevent, to a large extent, the DEM-induced reduction of DNA-binding activity at earlier time points, when the effect of DEM was stronger, but it depressed PPARalpha activity at later time points, when the effect of DEM was greatly reduced. CONCLUSION: A nutritional substance, such as RES, is able to influence the activity of gene-regulating factors, but the net effect is difficult to predict when the compound involved has multiple biological properties. Caution is therefore warranted before drawing conclusions about the potential benefits of RES for human health.