17β-estradiol mediated potentiation of sulforaphane effects on cardiac cells

ifferent studies demonstrated that female gender is associated with improved heart failure survival, and estrogens seem to play a fundamental role in this protection. It has been suggested that 17 β-estradiol (E2) reduces apoptosis in animal model of myocardial infarction through the modulation of MAPKs involved in oxidative stress1. Moreover recent evidences suggest that gender can influence the response to cardiovascular medications2,3. Therefore, we hypothesized that sex hormones could also modulate the cardioprotective effects of nutraceutical compounds, such as the isothiocyanate sulforaphane (SF), present in Brassica vegetables. In a previous study we evidenced that low concentrations of SF, in the presence of E2, counteracted oxidative damage better than SF alone. This effect seems to be related to the up-regulation of several antioxidant enzymes (GST, HO-1, GR, Trx, NQO1) and to the activation of pro-survival pathways (PI3K/Akt and ERK1/2). Aim of this study was to better clarify the mechanisms of E2-mediated potentiation of SF effects. H9c2 cardiomyoblasts were treated with SF in the absence/presence of E2 for different times. After 6h treatment, the co-treatment with SF and E2 induced a higher activation of Nrf2 transcription factor in respect to SF treatment alone. The study the involvement of E2 in SF induced Akt activation specific agonists for estrogen receptors were used. GPR30 (G protein-coupled receptor 30) and ER-ß (estrogen receptor beta) emerged to be involved in Akt activation. Moreover the co-treatment increased free [Ca++]I evaluated by Fura-2 probe suggesting its involvement in E2 mediated effects. Our results increase the knowledge on E2 mediated potentiation of SF effects in cardiac cells.