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Received for publication January 23, 2006.
Revised April 13, 2006.
Accepted for publication April 13, 2006.
-Estradiol and Non-feminizing Estrogens against H2O2 Toxicity in Human Neuroblastoma SK-N-SH cells
Neuroprotective effects of estrogens have been shown in various in vitro and in vivo models, but the mechanisms underlying estrogen protection are not clear. Mounting evidence suggest antioxidant effects contribute to the neuroprotective effects of estrogens. In the present study we assessed the protective effects of estrogens against H2O2-induced toxicity in human neuroblastoma cells and the potential mechanisms involved in this protection. We demonstrate that 17
-estradiol (17-E2) increases cell survival against H2O2 toxicity in human neuroblastoma cells. 17-E2 potentially reduced lipid peroxidation induced by 5 min H2O2 exposure. Further, 17-E2 exerts the protective effects by maintaining intracellular Ca2+ homeostasis, attenuating ATP depletion, ablating mitochondrial calcium overloading and preserving mitochondrial membrane potential. Two non-feminizing estrogens, 17
- and ent-estradiol, were as effective as 17-E2 in increasing cell survival, alleviating lipid peroxidation, preserving mitochondrial function, maintaining intracellular glutathione levels and Ca2+ homeostasis against H2O2 insult. Moreover, the ER antagonist, ICI 182,780, did not block effects of 17-E2, but increased cell survival and blunts intracellular Ca2+ increases. However, these estrogens failed to reduce cytosolic reactive oxygen species (ROS), even at concentrations as high as 10 µM. In conclusion, estrogens exert protective effects against oxidative stress by inhibiting lipid peroxidation and subsequently preserving Ca2+ homeostasis, mitochondrial membrane potential and ATP levels.
Key words:
Sex hormones, Ca imaging, Fluorescence techniques, Oxidative stress/antioxidants
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