Lithium induces ER stress and N-glycan modification in galactose-grown Jurkat cells

PLoS One. 2013 Jul 22;8(7):e70410. doi: 10.1371/journal.pone.0070410. Print 2013.

Abstract

We previously reported that lithium had a significant impact on Ca(2+) regulation and induced unfolded protein response (UPR) in yeast cells grown on galactose due to inhibition of phosphoglucomutase (PGM), however the exact mechanism has not been established yet. In this study, we analysed lithium's effect in galactose-fed cells to clarify whether these ER-related changes are the result of a relative hypoglycemic state. Furthermore, we investigated whether the alterations in galactose metabolism impact protein post-translational modifications. Thus, Jurkat cells were incubated in glucose or galactose containing media with or without lithium treatment. We found that galactose-fed and lithium treated cells showed better survivability than fasting cells. We also found higher UDP-Hexose and glycogen levels in these cells compared to fasting cells. On the other hand, the UPR (X-box binding protein 1 mRNA levels) of galactose-fed and lithium treated cells was even greater than in fasting cells. We also found increased amount of proteins that contained N-linked N-acetyl-glucosamine, similar to what was reported in fasting cells by a recent study. Our results demonstrate that lithium treatment of galactose-fed cells can induce stress responses similar to hypoglycemia, however cell survival is still secured by alternative pathways. We propose that clarifying this process might be an important addition toward the better understanding of the molecular mechanisms that regulate ER-associated stress response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Cell Proliferation / drug effects
  • Endoplasmic Reticulum Stress / drug effects*
  • Galactose / metabolism
  • Galactose / pharmacology*
  • Homeostasis / drug effects
  • Humans
  • Jurkat Cells
  • Lithium / pharmacology*
  • Phosphoglucomutase / metabolism
  • Polysaccharides / metabolism*
  • Unfolded Protein Response / drug effects

Substances

  • Polysaccharides
  • Lithium
  • Phosphoglucomutase
  • Calcium
  • Galactose

Grant support

This work was supported by Hungarian Fund OTKA (73591 and 78480) and by the Research Fund of the University of Pécs, Faculty of Medicine (ÁOK-KA 2013/19). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.