17-β-Estradiol Induces an Inhibitor of Active Caspases

摘要: We have shown previously that caspase-6 activity is lethal to human neurons (LeBlanc et al., 1999; Zhang 2000). Here we find 17-beta-estradiol but not 17-alpha-estradiol prevents caspase-6-mediated neuronal cell death. 17-beta-estradiol-treated extracts directly inhibit recombinant active caspase-6, caspase-3, caspase-7, and caspase-8 in vitro. conclude induces a caspase inhibitory factor (CIF) preventing apoptosis. The induction of CIF occurs within 10 min exposure neurons, does require de novo protein synthesis, involves mitogen-activated kinase activation. effect antagonized by the estrogen receptor antagonist tamoxifen. In contrast, induce or prevent caspase-mediated death cultured astrocytes. act through oxidation site. copurifies with proteins between 12 14 kDa size. Our results indicate an inhibitor caspases receptor-mediated nongenomic pathway provide additional mechanism for neuroprotective action likely highly relevant understanding role against Alzheimer's disease.