Estrogen effects in the myocardium: Inhibition of NF-κB DNA binding by estrogen receptor-α and -β

We have previously shown that estrogen effects in the heart include direct hormone effects on the myocardium. In a recent study we found that one beneficial effect of estradiol on the myocardium is the inhibition of apoptosis in cardiac myocytes. This effect was associated with a reduction of NF-κB activity. In the present study we have analyzed the functional mechanism of NF-κB inhibition in the myocardium by estrogen receptors-α and -β. Despite the previous finding that 17-β-estradiol (10 nM) inhibited the staurosporine-induced binding of p65/p50 NF-κB complexes to their cognate DNA elements in cultured rat cardiac myocytes, myocyte extracts showed no change in expression or cellular localization of p65, p50, and IκB upon staurosporine or estradiol treatment. Addition of either estrogen receptor-α or estrogen receptor-β as recombinant protein was sufficient to inhibit staurosporine-dependent p65/p50 DNA binding in cardiac myocytes. 17-β-Estradiol inhibits staurosporine-induced p65/p50 DNA binding associated with apoptotic cell death of cardiac myocytes via estrogen receptors-α and -β. This is not associated with changes in p65, p50 and IκB expression or subcellular localization. Thus, inhibition of NF-κB activity by estrogenic compounds might inhibit NF-κB dependent gene expression such as pro-inflammatory cytokines in the myocardium. © 2001 Academic Press.