title: 17β-estradiol prevents reduction of retinal phosphorylated 14-3-3 zeta protein levels following a neurotoxic insult.
abstract: Previous studies demonstrated the substantial protective role of 17β-estradiol (E2) in several types of neuron, although its mechanism of action remains to be elucidated. In this study, we found that the levels of 14-3-3 zeta mRNA and phosphorylated and total 14-3-3 zeta proteins were significantly decreased in the rat retina after intravitreal injection of N-methyl-d-aspartate (NMDA). 17β-E2 implantation significantly inhibited NMDA-induced decreases in phosphorylated but not in total 14-3-3 zeta protein levels in the retina. There was a decrease in both phosphorylated and total 14-3-3 protein levels in RGC-5 cells, a retinal ganglion cell line, after glutamate and buthionine sulfoximine (BSO) exposure, and 17β-E2 treatment significantly inhibited only the decrease in phosphorylated but not in total 14-3-3 zeta protein levels. The cell viability assay showed substantial cell death after glutamate and BSO exposure and that 17β-E2 treatment significantly protects against this cell death. 17β-E2 treatment also significantly increased the level of phosphorylated 14-3-3 protein in RGC-5 cells without other treatments. These results suggest that a decrease in 14-3-3 zeta expression may be associated with retinal neurotoxicity induced by NMDA or the combination of glutamate and BSO. The regulation of 14-3-3 zeta phosphorylation is one possible mechanism of the protective effect of 17β-E2 in the retina.
authors.affiliation: Department of Life Sciences, Toyo University, Oura, Gunma, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Koseki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaoka
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Munemasa
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumai
authors.forename: Kaori
authors.initials: K
authors.lastname: Kojima
authors.forename: Satoki
authors.initials: S
authors.lastname: Ueno
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Ohtani-Kaneko
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D058449:Intravitreal Injections; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D018696:Neuroprotective Agents; D004958:Estradiol; D016202:N-Methylaspartate