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Oestradiol or genistein rescues neurons from amyloid beta-induced cell death by inhibiting activation of p38
- Source :
- Aging cell. 7(1)
- Publication Year :
- 2007
-
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.
- Subjects :
- MAPK/ERK pathway
Aging
Programmed cell death
medicine.medical_specialty
Amyloid beta
Cell Survival
p38 mitogen-activated protein kinases
Genistein
Phytoestrogens
In Vitro Techniques
medicine.disease_cause
Neuroprotection
p38 Mitogen-Activated Protein Kinases
chemistry.chemical_compound
Internal medicine
medicine
Animals
Cells, Cultured
Cerebral Cortex
Neurons
Amyloid beta-Peptides
biology
Cell Death
Estradiol
Estrogens
Cell Biology
Glutathione
Mitochondria
Rats
Oxidative Stress
Endocrinology
chemistry
biology.protein
Oxidation-Reduction
Oxidative stress
Subjects
Details
- ISSN :
- 14749726
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Aging cell
- Accession number :
- edsair.doi.dedup.....11332338173d9a79e49f3b4b8b9b6d04