Abstract: ABSTRACT : Objective To investigate the role of oxidative stress in the expression of β-Amyloid precursor protein cleavage enzyme 1(BACE1) and the changes of DNA methylation and histone acetylation.Methods Cultured SH-SY5Y cells treated with H2O2 were used to test the expressions of BACE1, DNA methyltransferases 1, 3A (DNMT1,DNMT3A) and histone deacetyltranferase (HDAC) by Western blot. The level of mRNA of BACE1 was assessed by RT-PCR. Acetylation level of histone H3 and H4 were examined by optical density assay. Results Both BACE1 mRNA and protein levels were up-regulated significantly after H2O2 treatment for 1 and 72h; DNMT1 and DNMT3A expressions were decreased to 75% and 65% of control respectively after H2O2 treatment for 72h; HDAC3 level was increased as 1.6 folds as control; While the level of histone H3 acetylation was decreased and there was no change with histone H4 acetylation. Conclusion Oxidative stress may regulate BACE1 expression in SH-SY5Y through alteration of DNA methylation and histone acetylation which play a role in Alzheimer's disease(AD) pathogenesis.

Key words: Key words: Oxidative stress, β-Amyloid precursor protein cleavage enzyme 1 , DNA methylation, Histone acetylation, Alzheimer's disease