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

Abstract

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.

Cadmium stress: an oxidative challenge

“…Sheader et al (2006) confirm this hypothesis as they detected a strong upregulation of Prx after Cd exposure in Platichthys flesus. The oxidized form of Prx-3, on the other hand, seems to be involved in Cd-induced apoptosis in human neuroblastoma cells (Oh et al 2009). Thioredoxin (Trx) and glutaredoxin (Grx) are important compounds in the maintenance of the intracellular redox homeostasis and are kept in their reduced state via NADPH dependent thioredoxin reductases (TrxR) or GSH respectively (Meyer et al 2008).…”

“…Thioredoxin (Trx) and glutaredoxin (Grx) are important compounds in the maintenance of the intracellular redox homeostasis and are kept in their reduced state via NADPH dependent thioredoxin reductases (TrxR) or GSH respectively (Meyer et al 2008). Most studies indicate an enhanced oxidation of Trx1 and Trx2 redox states after Cd exposure (Hansen et al 2006;Oh et al 2009), resulting in apoptosis. This is probably due to an increased binding of Cd although a reduction in TrxR activity was also detected during Cd stress (Hodkova et al 2008).…”

Silencing of peroxiredoxin III inhibits formaldehyde‐induced oxidative damage of bone marrow cells in BALB/c mice

“…Scholars found that PrxIII appeared an enhanced expression in some cancers (such as prostate, endometrial, colorectal, etc. ), 19–22 and some environmental chemical pollutants (such as cadmium) also increased PrxIII expression 23 . Therefore, the enhanced expression of PrxIII is considered to be related to the occurrence of tumor 24 …”

“…), [19][20][21][22] and some environmental chemical pollutants (such as cadmium) also increased PrxIII expression. 23 Therefore, the enhanced expression of PrxIII is considered to be related to the occurrence of tumor. 24 Our previous research in vivo observed that FA caused oxidative damage of bone marrow cells of mice accompanied by high expression of PrxIII, at the same time the activities and expressional levels of caspase-3 and -9 were also observed increased, indicating that mitochondrial apoptosis pathway was occurred after FA exposure.…”