Na+/K+-ATPase level and products of lipid peroxidation in live cells treated with therapeutic lithium for different periods in time (1, 7, and 28 days); studies of Jurkat and HEK293 cells

Abstract

Regulation of Na+/K+-ATPase in bipolar disorder and lithium therapy has been investigated for more than 40 years. Contradictory results in this area may be caused by the difference between acute and long-term Li effects on cell metabolism and variance in responsiveness of different cell types. We compared the time-course of Li action focusing on Na+/K+-ATPase and lipid peroxidation in two widely different cell models–Jurkat and HEK293. Na+/K+-ATPase expression level was determined in cells cultivated in the absence or presence of 1 mM Li for different time spans (1, 7, and 28 days) using [3H] ouabain binding and immunoblot assay of α-subunit. In parallel samples, the formation of malondialdehyde (MDA) was quantified by HPLC, and 4-hydroxy-2-nonenal (4-HNE) protein adducts were determined by immunoblot. Cultivation of Jurkat cells in 1 mM Li medium resulted in downregulation of Na+/K+-ATPase (decrease of [3H] ouabain-biding sites and intensity of immunoblot signals) in all Li-groups. In HEK293 cells, the decrease of Na+/K+-ATPase was observed after the acute, 1-day exposure only. The long-term treatment with Li resulted in Na+/K+-ATPase upregulation. MDA and 4-HNE modified proteins were decreased in Jurkat cells in all Li-groups. On the other hand, in HEK293 cells, MDA concentration was decreased after the acute, 1-day Li exposure only; the long-term cultivations, for 7 or 28 days, resulted in a significant increase of lipid peroxidation products. The Li-induced decrease of lipid peroxidation products was associated with the decrease of Na+/K+-ATPase level and vice versa.

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Funding

This work was supported by the Czech Science Foundation GA CR (GA17-07070S), from the institutional project of the Institute of Physiology of the Czech Academy of Sciences (RVO:67985823) and from the institutional research plan of the Institute of Analytical Chemistry of the Czech Academy of Sciences (RVO:68081715).

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PS and MV conceived and designed research. MV, LR, HU, MH, and SM conducted experiments. MV, LR and PS analyzed data. MV, PS, and MA wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Miroslava Vosahlikova.

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Vosahlikova, M., Roubalova, L., Ujcikova, H. et al. Na+/K+-ATPase level and products of lipid peroxidation in live cells treated with therapeutic lithium for different periods in time (1, 7, and 28 days); studies of Jurkat and HEK293 cells. Naunyn-Schmiedeberg's Arch Pharmacol 392, 785–799 (2019). https://doi.org/10.1007/s00210-019-01631-4

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Keywords

  • Lithium
  • Na+/K+-ATPase
  • Lipid peroxidation products
  • Jurkat cells
  • HEK293 cells