Cellular resistance to cytotoxicity is conferred by various detoxification and antioxidant enzymes, including a family of cytosolic and microsomal glutathione transferases (GSTs). GST isoenzymes are involved in detoxification of xenobiotics, and play an important role in protecting cells against dietary mutagens and reactive oxygen species. Oxidants and oxidative stress activate microsomal GSTs (MGSTs), as well as cytosolic GSTs, which represents a major mechanism in protection against chemical stress. Cytosolic GSTA4-4 is believed to be the main glutathione transferase responsible for the cell defense against oxidative stress through its high activity for 4-hydroxynonenal and related endogenous electrophiles. The microsomal glutathione S-transferase 1 (MGST1) is the most active against harmful xenobiotics as well as metabolites produced during oxidative stress. Intracellular Ca²⁺ in neuronal cells is essential for excitability, synaptic plasticity and neurite outgrowth. Plasma membrane calcium ATPase (PMCA) is the most sensitive enzyme in decreasing of intracellular Ca²⁺ concentration. Whereas PMCA1 and 4 isoforms appear to be ubiquitous, PMCA2 and 3 are characteristic for excitable cells. In our laboratory we constructed stable-transfected PC12 cell lines with suppressed expression of PMCA2 or PMCA3 isoforms. We investigated the mRNA distribution and the specific activities of GSTA4 and MGST1 in cytoplasmic fraction of control PC12 cells and of stable-transfected cell lines. Preliminary studies on the expression of rGSTA4 and rMGST1 on mRNA level show that the expression of rGSTA4 is affected by the PMCA genes suppression as well as the expression of rMGST1 gene. The specific activity of both GSTs differed in cellular fractions of the tranfected cell lines comparing to the control cells. Our results indicate that in PC12 cells altered pattern of PMCA isoforms with concomitant disturbances of calcium homeostasis can influence the function of cellular GSTs.

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