Abstract
AIMS: Although oxidized low-density lipoprotein (ox-LDL) in the brain induces neuronal death, the mechanism underlying the damage effects remains largely unknown. Given that the ultimate outcome of a cell is depended on the balance between autophagy and apoptosis, this study was performed to explore whether ox-LDL induced HT-22 neuronal cell damage via autophagy impairment and apoptosis enhancement. METHODS: Flow cytometry and transmission electron microscopy (TEM) were used to evaluate changes in cell apoptosis and autophagy, respectively. The protein expression of LC3-II, p62, Bcl-2, and Bax in HT-22 cells was measured by Western bolt analysis. RESULTS: Our study confirmed that 100 μg/mL of ox-LDL not only promoted TH-22 cell apoptosis, characterized by elevated cell apoptosis rate and Bax protein expression, decreased Bcl-2 protein expression, and damaged cellular ultrastructures, but also impaired autophagy as indicated by the decreased LC3-II levels and the increased p62 levels. Importantly, all of these effects of ox-LDL were significantly aggravated by cotreatment with chloroquine (an inhibitor of autophagy flux). In contrast, cotreatment with rapamycin (an inducer of autophagy) remarkably reversed these effects of ox-LDL. CONCLUSIONS: Taken together, our results indicated that ox-LDL-induced shift from autophagy to apoptosis contributes to HT-22 cell damage.