4-Hydroxynonenal Induces Mitochondrial-Mediated Apoptosis and Oxidative Stress in SH-SY5Y Human Neuronal Cells

: Excessive and sustained increases in oxidative stress and apoptosis have been implicated in the pathogenesis of many diseases. In this study, we demonstrated that 4‐hydroxynonenal (4‐HNE), a product of lipid peroxidation in a range of concentration (0.1–50 μM) showed cytotoxic effects on SH‐SY5Y cell culture at a concentration >5 μM at 4 hr of exposure. 4‐HNE dose dependently decreased cell viability and significantly promoted reactive oxygen species formation and enhanced oxidative stress as reflected in the increased level of lipid peroxidation and catalase activity and decreased glutathione peroxidase activity as well as glutathione levels. 4‐HNE‐induced oxidative stress was associated with increased transcriptional and translational expressions of Bax and p53 in SH‐SY5Y cells. Mitochondrial‐mediated apoptosis was confirmed by increased expression and activity of caspase‐3. Our data demonstrate that 4‐HNE induces neuronal cell death through abnormal expression of apoptotic markers (p53, Bax and caspase‐3). Oxidative stress may be involved in the initial priming of SH‐SY5Y cells to 4‐HNE‐induced cytotoxicity in vitro.