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17β‐estradiol does not protect cerebellar granule cells from excitotoxicity or apoptosis
Author(s) -
Miñano Alfredo,
Cerbón Marco Antonio,
Xifró Xavier,
Malagelada Cristina,
Aguilera José,
RodríguezAlvarez José
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04475.x
Subject(s) - neuroprotection , excitotoxicity , microbiology and biotechnology , protein kinase b , extracellular , kinase , programmed cell death , ask1 , signal transduction , biology , glutamate receptor , apoptosis , protein kinase a , chemistry , mitogen activated protein kinase kinase , biochemistry , pharmacology , receptor
Mounting evidences have suggested that 17β‐estradiol (E2) could have a neuroprotective action in the CNS. In the present study, we wanted to study whether this estrogen was able to protect cerebellar granule cells (CGCs) from apoptosis or excitotoxicity. Our results suggest that E2 has no anti‐apoptotic effect in CGCs cultures. The lack of phosphoinositide 3‐kinase/Akt pathway activation in CGCs cultures could be on the basis of the failure of estradiol to protect CGCs from potassium‐deprivation and ceramide‐mediated apoptosis. Moreover, E2 does not protect CGCs from glutamate‐mediated death despite activating the extracellular signal regulated kinase kinase/extracellular signal regulated kinase pathway, which suggests that extracellular signal regulated kinase kinase/extracellular signal regulated kinase pathway activation is not sufficient to sustain an estrogen‐mediated neuroprotective effect in CGCs cultures. By contrast, we found that the estrogen had a significant neuroprotective effect against hydrogen peroxide‐mediated neuronal death. This effect was due to the antioxidant properties of the chemical structure of estradiol, as the biological inactive isomer 17α‐estradiol was also able to reduce hydrogen peroxide‐mediated neuronal death.