Low density lipoprotein increases amyloid precursor protein processing to amyloidogenic pathway in differentiated SH-SY5Y cells
Hypercholesterolemia has been considered as a risk factor for Alzheimer’s disease (AD). In addition to low density lipoprotein (LDL), oxidized LDL plays some roles in AD pathology. Neurodegenerative effect of oxidized LDL was supported by the increased oxidative stress in neurons. To further investigate the role of oxidized LDL, the present study aimed to test its effect on amyloid precursor protein (APP) processing. The release of soluble APP (sAPP) was evaluated in differentiated SH-SY5Y neuroblastoma cells exposed to native (non-oxidized) or oxidized human LDL including mildly and fully oxidized LDL (mox- and fox-LDL). Non-amyloidogenic and amyloidogenic pathways were investigated using specific antibody against sAPPα and sAPPβ. The results demonstrate that oxidized LDL induced neuronal death in dose-dependent patterns. Mox-LDL mediated caspase-3 dependent apoptosis, whereas fox-LDL notably damaged cell membrane. At subtoxic concentration, only native but not oxidized LDL induced the release of sAPP dominantly in amyloidogenic pathway with no change in β-secretase activity. These results suggest that LDL and oxidized LDL play critical roles in AD pathogenesis via different pathways. Elevated serum LDL level together with high oxidative stress may aggravate the progression of AD.
Key wordsAlzheimer’s disease low density lipoprotein oxidized LDL amyloid precursor protein β-secretase
A disintegrin and metalloproteinases
amyloid precursor protein
β-site APP cleaving enzyme 1
foetal bovine serum
fully oxidized-low density lipoprotein
mildly oxidized-low density lipoprotein
soluble amyloid precursor protein alpha
soluble amyloid precursor protein beta
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