Elevation of intracellular Na+ contributes to expression of early response genes triggered by endothelial cell shrinkage

Alexandra A. Shiyan, Svetlana V. Sidorenko, Dmitry Fedorov, Elizaveta A. Klimanova, Larisa V. Smolyaninova, Leonid V. Kapilevich, Ryszard Grygorczyk, Sergei N. Orlov

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Background/Aims: Prolonged hyperosmotic shrinkage evokes expression of osmoprotective genes via nuclear factor NFAT5-mediated pathway and activates Na+ influx via hypertonicity-induced cation channels (HICC). In human umbilical vein endothelial cells (HUVEC) elevation of intracellular sodium concentration ([Na+]i) triggers transcription of dozens of early response genes (ERG). This study examined the role of monovalent cations in the expression of Na+ isensitive ERGs in iso- and hyperosmotically shrunken HUVEC. Methods: Cell volume was measured by 3D reconstruction of cell shape and as 14C-urea available space. Intracellular Na+ and K+ content was measured by flame atomic absorption spectrometry. ERG transcription was estimated by RT-PCR. Results: Elevation of medium osmolality by 150 mM mannitol or cell transfer from hypo- to isosmotic medium decreased cell volume by 40-50%. Hyperosmotic medium increased [Na+]i by 2-fold whereas isosmotic shrinkage had no impact on this parameter. Hyperosmotic but not isosmotic shrinkage increased up-to 5-fold the content of EGR1, FOS, ATF3, ZFP36 and JUN mRNAs. Expression of these ERGs triggered by hyperosmotic shrinkage and Na+,K+-ATPase inhibition by 0.1 µM ouabain exhibited positive correlation (R2=0.9383, p=0.0005). Isosmotic substitution of NaCl by N-methyl-D-glucamine abolished an increment of [Na+]i and ERG expression triggered by mannitol addition. Conclusion: Augmented expression of ERGs in hyperosmotically shrunken HUVEC is mediated by elevation of [Na+]i

Original languageEnglish
Pages (from-to)638-647
Number of pages10
JournalCellular Physiology and Biochemistry
Issue number4
Publication statusPublished - 2019


  • Cell shrinkage
  • Early response genes
  • Endothelium
  • Intracellular Na
  • Ouabain
  • Transcription

ASJC Scopus subject areas

  • Physiology

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