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

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&...

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Bibliographic Details
Published in:	PloS one Vol. 8; no. 7; p. e70410
Main Authors:	Nagy, Tamás, Frank, Dorottya, Kátai, Emese, Yahiro, Rikki K K, Poór, Viktor S, Montskó, Gergely, Zrínyi, Zita, Kovács, Gábor L, Miseta, Attila
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 22-07-2013 Public Library of Science (PLoS)
Subjects:	Activating transcription factor 1 Alzheimer's disease Baking yeast Biology Bipolar disorder Calcium Calcium - metabolism Carbohydrates Cell Proliferation - drug effects Cell survival Endoplasmic Reticulum Stress - drug effects Fasting Galactose Galactose - metabolism Galactose - pharmacology Glucosamine Glucose Glycan Glycogen Hexose Homeostasis Homeostasis - drug effects Humans Hypoglycemia Jurkat Cells Kinases Laboratories Laboratory testing Lactose Lithium Lithium - pharmacology Medicine Metabolism Metabolites Molecular modelling mRNA N-Acetylglucosamine Phosphatase Phosphoglucomutase Phosphoglucomutase - metabolism Polysaccharides - metabolism Post-translation Protein binding Protein folding Protein turnover Proteins Saccharomyces cerevisiae Stress Stresses Survivability Unfolded Protein Response - drug effects Hungary
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Summary:	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.
Bibliography:	Conceived and designed the experiments: TN DF GLK AM. Performed the experiments: TN DF EK RKKY VSP GM ZZ. Analyzed the data: TN DF AM. Contributed reagents/materials/analysis tools: GM GLK. Wrote the paper: TN DF AM. Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0070410