Oestradiol or genistein rescues neurons from amyloid beta-induced cell death by inhibiting activation of p38.
Aging Cell
; 7(1): 112-8, 2008 Jan.
Article
em En
| MEDLINE
| ID: mdl-18031570
ABSTRACT
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-beta estradiol (0.2 nm) or with nutritionally relevant concentrations of genistein (0.5 microm), and 48 h later treated with 5 microm of amyloid beta (Abeta) for 24 h. We found that Abeta 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 Abeta. All these effects were prevented when cells were pretreated for 48 h with oestradiol or genistein. Therefore, oestrogenic compounds rescue neurons from Abeta-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 Abeta-associated neurodegenerative disorders should be more carefully studied in clinical research.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
/
Morte Celular
/
Genisteína
/
Proteínas Quinases p38 Ativadas por Mitógeno
/
Fitoestrógenos
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Estradiol
/
Estrogênios
/
Neurônios
Idioma:
En
Revista:
Aging Cell
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Espanha