17 beta-Estradiol protects lymphocytes against dopamine and iron-induced apoptosis by a genomic-independent mechanism Implication in Parkinson's disease

Dopamine (DA) in combination with iron (Fe2+) has been demonstrated to indu ce apoptosis in neuronal-like PC12 cells by an oxidative stress mechanism. To get a better insight of cell death and protective mechanisms in DA/Fe2+- induced toxicity, we investigated the effects of DA/Fe2+ and the antioxidan t action of 17 beta -estradiol (E2) in peripheral blood lymphocytes (PBL). We found that DA/Fe2+-induces apoptosis in PBL via a hydrogen peroxide (H2O 2)-mediated oxidative mechanism, which in turn triggers a cascade of molecu lar events requiring RNA and de novo protein synthesis. We have also demons trated that E2 prevents significantly DA/Fe2+-induced apoptosis in PBL by d irectly inhibiting the intracellular accumulation of peroxides generated by DA/Fe2+-reaction. This protective activity is independent of the presence or activation of the estrogen receptors (ERs). These data further support a nd validate our previous hypothesis that DA/Fe2+/H2O2 could be a general me diator of oxidative stress through a common cell death mechanism in both ne uronal and nonneuronal cells. These findings may be particularly relevant t o the potential approaches to rescue and prolong the survival of neurons by estrogens in patients with Parkinson's disease (PD). (C) 2001 Elsevier Sci ence Inc. All rights reserved.