Estudios científicos

The dietary antioxidant resveratrol affects redox changes of PPARalpha activity


BACKGROUND AND AIMS: 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.

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Antecedentes y objetivos: la interacción gen-ambiente está detrás de la patogénesis de las enfermedades más extendidas y la nutrición es uno de los factores ambientales de mayor impacto en la salud humana. Los mecanismos involucrados en la interacción entre los factores nutricionales y el fondo genético de las personas aún no están claros. El objetivo de este estudio fue investigar si el resveratrol (RES), un polifenol antioxidante del vino tinto, puede influir en la actividad de PPARalpha en la línea de células de hepatoma de rata McArdle-RH7777. PPARalpha es un factor de transcripción que regula la expresión de genes cuando se activan por medio de ácidos grasos endógenos o exógenos de cadena larga. Sus resultados en la activación de una protección significativa a causa de enfermedades cardiovasculares en humanos.