Resveratrol has beneficial effects on aging, inflammation and
metabolism, which are thought to result from activation of the lysine
deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated
protein kinase. Here we report that resveratrol acts as a
pathway-selective estrogen receptor-α (ERα) ligand to modulate the
inflammatory response but not cell proliferation. A crystal structure of
the ERα ligand-binding domain (LBD) as a complex with resveratrol
revealed a unique perturbation of the coactivator-binding surface,
consistent with an altered coregulator recruitment profile. Gene
expression analyses revealed significant overlap of TNFα genes modulated
by resveratrol and estradiol. Furthermore, the ability of resveratrol
to suppress interleukin-6 transcription was shown to require ERα and
several ERα coregulators, suggesting that ERα functions as a primary
conduit for resveratrol activity.
See Scripps News Release
metabolism, which are thought to result from activation of the lysine
deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated
protein kinase. Here we report that resveratrol acts as a
pathway-selective estrogen receptor-α (ERα) ligand to modulate the
inflammatory response but not cell proliferation. A crystal structure of
the ERα ligand-binding domain (LBD) as a complex with resveratrol
revealed a unique perturbation of the coactivator-binding surface,
consistent with an altered coregulator recruitment profile. Gene
expression analyses revealed significant overlap of TNFα genes modulated
by resveratrol and estradiol. Furthermore, the ability of resveratrol
to suppress interleukin-6 transcription was shown to require ERα and
several ERα coregulators, suggesting that ERα functions as a primary
conduit for resveratrol activity.
See Scripps News Release
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