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

Abstract

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.