Acrolein, a highly reactive α,β-unsaturated
aldehyde, is a toxic component of cigarette
smoke. As a lipid peroxidation
biomarker,
acrolein plays an important role in a wide variety of disease states, such as neurodegenerative,
Alzheimer's disease, diabetes and
atherosclerosis. Endothelial cell injury is one of the initiating factors of
atherosclerosis, but the underlying molecular mechanisms remain unclear. Our study primarily focused on
acrolein-induced autophagy-dependent apoptosis and the possible molecular mechanism. The results showed that treatment with
acrolein increased the number of intracellular GFP-LC3 II punctuates and the expression of autophagosome
biomarker LC3-II, with the low dose (25 μM) or at the early stage of treatment (3 h). Following treatment of EAhy926 cells with
acrolein for 6 h, lysosomal permeabilization changed, and
cathepsin B (CB) was released. Additionally,
acrolein induced the collapse of mitochondrial transmembrane potential, and
cytochrome c was released. Furthermore,
caspase-3 and
caspase-9 activation showed that
acrolein induced EAhy926 cell apoptosis. Autophagy inhibitor 3MA and CB inhibitor
CA-074 Me (CA) attenuated
acrolein-induced apoptosis. Collectively, our results suggested that
acrolein-induced apoptosis is autophagy-dependent, occurring via injury to lysosomes and mitochondria. This study provides new mechanistic insight toward understanding the pathogenesis of
acrolein-related disorders.