Glutathione is present in abundance in the nervous system and plays a crucial role in multitude of biochemical processes. It can act as an antioxidant and participate in detoxification of xenobiotics or metabolic regulations. Under oxidative stress, including Ca²⁺ ­- induced events, GSH acts as a free radical scavenger and is reversibly oxidized to GSSG. In the cells, there are several systems responsible for maintaining the proper Ca²⁺ gradients across the membranes, and among them PMCA appears the most important. The enzyme is coded by four genes, and in nervous tissue PMCA2 and PMCA3 are thought to play the specific functions. The aim of presented study was to investigate the relationship between calcium homeostasis and metabolism of glutathione under stress conditions. We analyzed the total glutathione and GSH/GSSG ratio in the stable-transfected PC12 cell lines with suppressed expression of PMCA2, PMCA3, or both neuron-specific isoforms. The results showed differences in total glutathione concentrations in all examined PC12 cell lines. Altered calcium homeostasis caused significant decrease in the total glutathione concentration, and this effect was the most pronounced in the PC12 line with suppressed expression of both PMCA isoforms. Whereas the oxidized glutathione level decreased in all transfected PC12 cells when compared with a control line, there were not significant differences in GSH/GSSG ratio between studied cell lines. Our results suggest that affected calcium homeostasis can implicate depletion in glutathione level in PC12 cells. Since PC12 cells with suppressed PMCA isoforms maintain similar GSH/GSSG ratio, we conclude that they can not efficiently reduce GSSG, but they still preserve ability to throw out oxidized glutathione outside of the cell.

Supported by the grants No: PBZ-MIN-012/P04/2004 and 2/P05A/03529 from the Ministry of Education and Science, and 503-6086-02 from the Medical University of Lodz.

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