Effects and possible mechanisim of 17α-estradiol on the release of β-amyloid protein with the transgenic cell strain APP/PS1 N2a

Objective To investigate the effects of 17α-estradiol (E 2α) on the release of ß-amyloid protein (Aβ) with the transgenic cells β-amyloid precursor protein( APP)/ presenilin-1 ( PS1 )Neuro-2a (N2a) , and explore the potential mechanism of such effect. Methods APP/PS1 N2a cells were pretreated with 10×10 -9mol/L E2α for 2 days, then changed the culture medium, and treated with different methods: 1. Cells were treated with either E2α(25 nmol/L, 50 nmol/L, 100 nmol/L, 200 nmol/L)or vehicle, the protein level of Aβ and β;-secretase-1 ( BACE1 ) both intracellular and extracellular of APP/PS1 N2α cells were detected by Western blotting. 2. Cells were treated with 100 nmol/L E 2α, 20 nmol/L glucose and 5 IU glucose oxidase(GOX) , followed by exposure to the glucose oxidase (G/Gox) to induce oxidative stress. After 24 hours, the change of the Reactive oxygen species( ROS) contents in APP/PS1 N2a cells was observed for dihydroethidium( DHE). Results The extracellular level of Aß in APP/PS 1 N2a cells treated with various concentration (25 nmol/L,50 nmol/L,100 nmol/L,200 nmol/L/L) E 2αwere significantly decreased( P <0. 05 ) . There was no change in the intracellular levels of Aβ and the levels of BACE1(P > 0. 05 ). E2α reduced the ROS produced by APP/PS1 N2a cells after G/Gox treatment. Conclusion E2a may reduce the production of extracellular Aβ and its mechanism may be related to the oxidation damage.