Gadd153 Mediates 27-OHC-Induced AD Pathology Figure 2. siRNA to gadd153 reduces 27-OHC-induced increase in Ab production and tau phosphorylation. 27-OHC significantly increased levels of both secreted Ab40 and Ab42, and treatment with siRNA, alone or in presence of 27-OHC, significantly reduced Ab40 and Ab42 levels (a,b). siRNA to gadd153 also reduced 27-OHC-induced increase in APP and BACE1 levels (c–e). Note that siRNA to gadd153 markedly reduced basal levels of BACE1, suggesting that gadd153 regulates BACE1 transcription (c,e). Treatment with 27-OHC also increases phosphorylation of tau as detected with PHF-1 and CP13 antibodies (f–h). The increase in phosphorylated tau is reduced by treatment with siRNA to gadd153. *p,0.05, **p,0.01 and ***p,0.001 versus controls; #p,0.05, ##p,0.01 and ###p,0.001 versus 27-OHC. doi:10.1371/journal.pone.0026420.g002 the levels of ROS, H2O2 and 8-iso-PGF2a, it significantly reduced 27-OHC-induced increase in levels of these oxidative stress markers. Interestingly, as it was the case with BACE1 and Bcl-2, treatment with siRNA to gadd153 alone markedly increased glutathione levels in comparison to levels in control untreated slices. Additionally, siRNA to gadd153 reversed the depletion of PLoS ONE | www.plosone.org 5 October 2011 | Volume 6 | Issue 10 | e26420