![]() ![]() Collectively, our results suggest that under stress conditions, reduced seladin-1 expression results in enhanced GGA3 depletion, which further leads to augmented post-translational stabilization of BACE1 and increased β-amyloidogenic processing of APP. No changes in GGA3 or BACE1 levels were found after seladin-1 knockdown in normal growth conditions. These adverse changes associated with decreased cell viability in seladin-1 siRNA-transfected cells under apoptosis. Augmented BACE1 activity in turn correlated with the enhanced β-amyloidogenic processing of APP and ultimately increased Aβ production. ![]() Increased caspase-3 activity coincided with a significant depletion of the BACE1-sorting protein, GGA3 (Golgi-localized γ-ear-containing ADP-ribosylation factor-binding protein), and subsequently augmented BACE1 protein levels and activity. However, under apoptosis, seladin-1 small interfering RNA (siRNA)-transfected cells showed increased caspase-3 activity on average by 2-fold when compared with control siRNA-transfected cells. Our results show that ∼60% reduction in seladin-1 protein levels, resembling the decrease observed in AD brain, did not significantly affect APP processing or Aβ secretion in normal growth conditions. Here, we have employed RNA interference to assess the molecular effects of seladin-1 down-regulation on the β-secretase (BACE1) function and β-amyloid precursor protein (APP) processing in SH-SY5Y human neuroblastoma cells in both normal and apoptotic conditions. Seladin-1 protects cells against β-amyloid (Aβ) peptide 42- and oxidative stress-induced apoptosis activated by caspase-3, a key mediator of apoptosis. Seladin-1 is a neuroprotective protein selectively down-regulated in brain regions affected in Alzheimer disease (AD). ![]()
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