Involvement of Oxidized Peroxiredoxin-3 in Cadmium- and Ceramide-induced Apoptosis of Human Neuroblastoma Cells

Cadmium (Cd) is an environmental pollutant that produces numerous toxic effects in humans. Previous reports have demonstrated that Cd induces neurodegeneration and other diseases. To study the mechanism of Cd-induced neurodegeneration, SH-SY5Y cells were exposed to Cd. Cd-induced ceramide production was observed in the cells in a time- and dose-dependent manner. Ceramide is a well known lipid second messenger. Previous reports have shown that accumulation of ceramide, triggered by oxidative stress or anticancer drugs, induces apoptosis. To identify proteins involved in cellular responses to Cd or ceramide, we performed comparative proteome analysis using high-resolution two-dimensional gel electrophoresis (2-DE). Four different proteins were identified by combination of mass spectrometry and peptide fingerprinting. Among them, the level of oxidized peroxiredoxin-3 (Prx-3) simultaneously increased in Cd- and ceramide-exposed cells. Furthermore, we observed Cd- or ceramide-induced generation of reactive oxygen species (ROS), leading to SH-SY5Y cell apoptosis. Pretreatment with Trolox helped scavenge Cd- or ceramide-induced ROS and prevented apoptosis, suggesting that Cd- or ceramide-induced cell death can be attributed to ROS production. Here, we elucidate the link between Cd-induced apoptosis and ROS scavenger system in SH-SY5Y cells.