Open AccessOestradiol or genistein rescues neurons from amyloid beta‐induced cell death by inhibiting activation of p38
Author(s) -
Vallés Soraya L.,
Borrás Consuelo,
Gambini Juan,
Furriol Jessica,
Ortega Angel,
Sastre Juan,
Pallardó Federico V.,
Viña Jose
Publication year - 2008
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2007.00356.x
Subject(s) - genistein , neuroprotection , programmed cell death , oxidative stress , p38 mitogen activated protein kinases , biology , glutathione , amyloid beta , kinase , microbiology and biotechnology , pharmacology , protein kinase a , biochemistry , endocrinology , apoptosis , enzyme , peptide
Summary Oestrogenic compounds have been postulated as neuroprotective agents. This prompted us to investigate their mechanism action in neurons in primary culture. Cells were pretreated with physiological concentrations of 17‐β estradiol (0.2 n m ) or with nutritionally relevant concentrations of genistein (0.5 µ m ), and 48 h later treated with 5 µ m of amyloid beta (Aβ) for 24 h. We found that Aβ increased oxidative stress, measured as peroxide levels or oxidized glutathione/reduced glutathione ratio, which in turn, caused phosphorylation of p38 MAP kinase. Amyloid beta subsequently induced neuronal death. Inhibiting the MAP kinase pathway prevented cell death, confirming the role of p38 in the toxic effect of Aβ. All these effects were prevented when cells were pretreated for 48 h with oestradiol or genistein. Therefore, oestrogenic compounds rescue neurons from Aβ‐induced cell death by preventing oxidative stress, which in turn inhibits the activation of p38, protecting neurons from cell death. Because hormone replacement therapy with oestradiol could cause serious setbacks, the potential therapeutic effect of phyto‐oestrogens for the prevention of Aβ‐associated neurodegenerative disorders should be more carefully studied in clinical research.