Abstract：
:Earlier studies showed that endogenous estrogens have neuroprotective effect against oxidative damage. The present study seeks to investigate the protective effect of various endogenous estrogen metabolites against oxidative neurotoxicity in vitro and in vivo. Using immortalized mouse hippocampal neuronal cells as an in vitro model, 4-hydroxyestrone, an estrone metabolite with little estrogenic activity, is found to have the strongest neuroprotective effect against oxidative neurotoxicity among 25 endogenous estrogen metabolites tested, and its protective effect is stronger than 17β-estradiol. Similarly, 4-Hydroxyestrone also exerts a stronger protective effect than 17β-estradiol against kanic acid-induced hippocampal oxidative damage in rats. Neuroprotection by 4-hydroxyestrone involves increased cytoplasmic translocation of p53 resulting from SIRT1-mediated deacetylation of p53. Analysis of brain microsomal enzymes shows that estrogen 4-hydroxylation is the main metabolic pathway in the central nervous system. Together, these results show that 4-hydroxyestrone is an endogenous neuroestrogen that can strongly protect against oxidative neuronal damage.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Choi HJ,Lee AJ,Kang KS,Song JH,Zhu BTdoi
10.1038/s41598-020-62984-ysubject
Has Abstractpub_date
2020-04-29 00:00:00pages
7283issue
1issn
2045-2322pii
10.1038/s41598-020-62984-yjournal_volume
10pub_type
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