title: 17beta-estradiol does not protect cerebellar granule cells from excitotoxicity or apoptosis.
abstract: Mounting evidences have suggested that 17beta-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 17alpha-estradiol was also able to reduce hydrogen peroxide-mediated neuronal death.
authors.affiliation: Institut de Neurociencies i Department Bioquímica i Biología Molecular, Universitat Autònoma de Barcelona, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Miñano
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Cerbón
authors.forename: Xavier
authors.initials: X
authors.lastname: Xifró
authors.forename: Cristina
authors.initials: C
authors.lastname: Malagelada
authors.forename: José
authors.initials: J
authors.lastname: Aguilera
authors.forename: José
authors.initials: J
authors.lastname: Rodríguez-Alvarez
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011960:Receptors, Estrogen; D018698:Glutamic Acid; D004958:Estradiol; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases