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Identification of a molecular mechanism underlying estrogen‐mediated neuroprotection in neuronal cells against oxidative stress
Author(s) -
Park Sookyoung,
Won Jinyoung,
Hong Yonggeun
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.693.1
Subject(s) - neuroprotection , oxidative stress , microbiology and biotechnology , gene knockdown , viability assay , biology , apoptosis , telomerase , programmed cell death , transfection , chemistry , cell culture , pharmacology , endocrinology , biochemistry , gene , genetics
Estrogen (17β‐estradiol; E2) has neuroprotective effects in the setting of CNS injury and neurodegenerative disorders however, the mediator for neuroprotection mechanisms by E2 remains largely unknown. Recent studies have demonstrated that E2 might be potent modulator of both expression and activity of telomerase, which is a ribonucleoprotein complex involved in maintenance of the chromosome end and DNA repair. To examine whether E2 treatment exerts cytoprotective effects in neuronal cells, mouse origin neuroblastoma Neuro‐2a (N2a) cells were differentiated into cholinergic phenotypes, and used as cell culture model following exposure to hydrogen peroxide to induce oxidative stress. Neuronal cell death was induced and morphologic changes were observed following oxidative stress. In addition, apoptotic changes including Bax:Bcl‐2 ratio and apoptosis‐related proteases caspase‐3 were increased in neuronal cells rendered by oxidative stress. E2 treatment attenuated these changes, as well as increased cell viability. Our data demonstrated that E2 treatment significantly increased TERT expression in a dose‐dependent manner in neuronal cells. To confirm whether the estrogen signaling is associated with TERT, selective siRNA targeted against both ERα and ERβ were transfected to neuronal cells. TERT mRNA expression was down‐regulated in both ERα and ERβ‐silenced neuronal cells in particular, this change was more distinctive in knockdown of ERα. Taken together, these findings indicate that the telomerase enzyme may be an important mediator of the neuroprotective effects of E2. Support or Funding Information NRF‐2013R1A2A2A01067169 to Y.H., NRF‐2014R1A1A3051724 to S.P., Republic of Korea.