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

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Abstract

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

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About the authors

O. E. Kvitko

Lomonosov Moscow State University

Author for correspondence.
Email: klimanova.ea@yandex.ru
Russian Federation, 119234, Moscow

D. A. Fedorov

Lomonosov Moscow State University

Email: klimanova.ea@yandex.ru
Russian Federation, 119234, Moscow

S. V. Sidorenko

Lomonosov Moscow State University

Email: klimanova.ea@yandex.ru
Russian Federation, 119234, Moscow

O. D. Lopina

Lomonosov Moscow State University

Email: klimanova.ea@yandex.ru
Russian Federation, 119234, Moscow

E. A. Klimanova

Lomonosov Moscow State University

Email: klimanova.ea@yandex.ru
Russian Federation, 119234, Moscow

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2. Fig. 1. The effect of 40 mM LiCl, 40 mM NaCl and 1.2 micrograms/ml of monenzine added to the culture medium on the intracellular content of Na+ (a), K+(b) and Li+ (c) ions in HUVEC. The cells were incubated under experimental conditions for 1.5 hours. The values are presented as the average ± SE (n = 4-6). Significant differences were calculated using a one-way ANOVA; * p < 0.05; *** p < 0.001; **** p < 0.0001

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3. Fig. 2. The dependence of intracellular Na+ content in HUVEC on the concentration of monensin in the culture medium. The cells were incubated in a monensin-containing medium for 1.5 hours. The values are presented as the average ± SE (n = 4-6)

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4. Fig. 3. The effect of 40 mM LiCl, 40 mM NaCl and 1.2 micrograms/ml of monenzine added to the culture medium on the mRNA content of the FOS (a), JUN(b), EGR1 (c), MYC (d), ATF3 (e), PTGS2 (e) genes in HUVEC. The cells were incubated under experimental conditions for 1.5 hours. The values are presented as the average ± SE (n = 5). Significant differences were calculated using a one-way ANOVA; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001

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