Mitochondrial damage precedes the changes of glutathione metabolism in CdCl2 treated neuronal SH-SY5Y cells

Abstract

Cadmium crosses the blood-brain barrier inducing damage to neurons. Cell impairment is predominantly linked to oxidative stress and glutathione (GSH) depletion. On the other hand, several reports have described an increase of GSH levels in neuronal cells after CdCl2 exposure. Therefore, the aim of the present report was to investigate the relation between changes in GSH levels and mitochondrial damage in neuronal cells after CdCl2 treatment. To characterize neuronal impairment after CdCl2 treatment (0–200 μM) for 1–48 h, we used the SH-SY5Y cell line. We analyzed GSH metabolism and determined mitochondrial activity using high-resolution respirometry. CdCl2 treatment induced both the decreases and increases of GSH levels in SH-SY5Y cells. GSH concentration was significantly increased in cells incubated with up to 50 μM CdCl2 but only 100 μM CdCl2 induced GSH depletion linked to increased ROS production. The overexpression of proteins involved in GSH synthesis increased in response to 50 and 100 μM CdCl2 after 6 h. Finally, strong mitochondrial impairment was detected even in 50 μM CdCl2 treated cells after 24 h. We conclude that a significant decrease in mitochondrial activity can be observed in 50 μM CdCl2 even without the occurrence of GSH depletion in SH-SY5Y cells.