Palmitate induced ER stress-mediated neurotoxicity in SH-SY5Y cells

Recent studies have indicated an association between obesity and neurodegenerative disease including Alzheimer’s disease. Palmitate, a representative circulating saturated fatty acid in obese patient, is considered as a candidate mediator of neurotoxicity as in peripheral tissues. Therefore, we investigated the underlying mechanism involved in palmitate-induced lipotoxicity using SH-SY5Y human neuroblastoma cells. Palmitate treatment significantly increased caspase-3 activity and apoptotic body staining. Endoplasmic reticulum (ER) stress was significantly induced by palmitate reflected in the increased mRNA level of spliced X box-binding protein-1. Palmitate activated c-jun N terminal kinase, a known mediator of apoptosis and tau phosphorylation in response to ER stress, resulting in tau hyperphosphorylation in SH-SY5Y cells. Palmitate significantly repressed the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase, suggesting an impairment in fatty acid oxidation. However, we did no...