The dietary antioxidant resveratrol affects redox changes of PPARalpha activity
Nutr Metab Cardiovasc Dis. 2007 May;17(4):247-56
Iannelli P, Zarrilli V, Varricchio E, Tramontano D, Mancini FP.
Department of Biological and Environmental Sciences, University of Sannio, via Port'Arsa 11, 82100 Benevento, Italy.
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.