In vitro neurodegeneration model: dopaminergic toxin-induced apoptosis in human SH-SY5Y cells

Abstract

The brains of patients with Parkinson's disease (PD) show evidence that mitochondrial complex I is suppressed. Therefore, it is considered that rotenone, a specific inhibitor of mitochondrial complex I, is a useful tool in animal models of PD. However, the mechanism of rotenone-induced neuronal death is not fully understood. In human SH-SY5Y cells, rotenone induced the degradation of caspases-9 and -3, followed by cleavage of poly(ADP-ribose) polymerase, DNA fragmentation and cell death. At that time, we detected a caspase-12-like protein (casp-12LP) that has a molecular mass (about 60 kDa) similar to that of mouse caspase-12, and it was degraded by rotenone, like an endoplasmic reticulum (ER) stress. Pretreatment with phorbol-12-myristate-13-acetate inhibited the rotenone-induced decrease in caspases-9 and -3, but not that in casp-12LP. In contrast, nonselective caspase inhibitor z-VAD.fmk inhibited the decrease in casp-12LP, but not those in caspases-9 and -3 in this study. These results suggest that rotenone-induced apoptosis may be mediated through both mitochondria- and ER-dependent pathways in human SH-SY5Y cells.