Accumulation of Li⁺ Ions Triggers Changes in FOS, JUN, EGR1, and MYC Transcription in the LiCl-Treated Human Umbilical Vein Endothelial Cells (HUVEC)

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Olga E. Kvitko^1#, Dmitrii A. Fedorov^1#, Svetlana V. Sidorenko¹, Olga D. Lopina¹, Elizaveta A. Klimanova^1,a*

¹Department of Biochemistry, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia

^* To whom correspondence should be addressed.

^# These authors contributed equally to the work.

Received: August 14, 2024; Revised: September 26, 2024; Accepted: September 30, 2024

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Changes in intracellular concentrations of Na⁺ and K⁺ are shown to alter gene expression. Another monovalent cation, Li⁺, is well known as a medicine for treatment of psychiatric disorders, but mechanism of its action is obscure. Thus, it is important to evaluate the effect of Li⁺ on gene expression in endothelial cells. Here we studied influence of the increased intracellular Na⁺ or Li⁺ concentrations on transcription of Na⁺_i/K⁺_i-sensitive genes. Treatment of the human endothelial cells (HUVEC) with LiCl for 1.5 h resulted in accumulation of Li⁺ in the cells. This was followed by increase in the FOS and EGR1 mRNAs levels and decrease in the JUN and MYC mRNA levels. Treatment of HUVEC with the Na⁺-ionophore monensin led to accumulation of Na⁺ and loss of K⁺ ions. However, monensin had no significant effect on gene expression. Incubation of HUVEC with elevated extracellular NaCl concentration increased intracellular K⁺ concentration and transcription of the ATF3 gene, while transcription of the JUN gene decreased. These results indicate that Na⁺ and Li⁺ ions have different effects on the gene expression profile in the cells that is likely associated with the fact that they affect differently the intracellular monovalent cations ratio.

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KEY WORDS: lithium, sodium, Na⁺/K⁺-sensitive genes, monensin, endothelial cells

DOI: 10.1134/S0006297924100146

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