In Saccharomyces cerevisiae the attenuation of the 2- deoxy-D-glucose toxicity is alleviated by inositol
Keywords:
2-deoxy-D-glucose, INO1, β-Galactosidase activity, over production of inositolAbstract
In Saccharomysis cerevasiae the glycolytic transcription factor GCR1 tightly controls the expression of genes involved in glycolysis but the importance of Gcr1 transcription in 2-DG toxicity is still elusive. In the present study, we observed 2-DG toxicity in the wild-type, gcr1∆, and ino2∆ cells under inositol absence (I−) condition obstruct the growth, hence the opi1∆ cells were resistant to 2-DG exposure. Further, the presence of 2-DG significantly decreased the promoter activity of INO1 in the WT cells. The 2-DG exposure suppressed the growth rate in WT and gcr1∆ strains under inositol limitation condition, but the opi1∆ (over production of inositol) strain was resistant to the 2-DG exposure with I− condition. Taken together, the above findings suggest that 2-DG exposure reduced the promoter activity of INO1 leads to inositol auxotrophic growth defect, hence the inositol supplementation bring back normal. To conclude that the inositol alleviates the 2-DG toxicity in Saccharomyces cerevisiae.
References
P. Biely, Z. Kratky, J. Kovařík, Š. Bauer, “Effect of 2-Deoxyglucose on cell wall formation in Saccharomyces cerevisiae and its relation to cell growth inhibition”, J Bacteriol, Vol.107, Issue.1, pp 121–129, 1971.
Z. Kratky, P. Biely, S. Bauer, “Mechanism of 2-Deoxy-d-glucose inhibition of cell-wall polysaccharide and glycoprotein biosynthesis in Saccharomyces cerevisiae”, Eur J Biochem, Vol.54, Issue.2, pp 459-67, 1975.
K.A. Willis, K.E. Barbara, B.B. Meno, J. MoVat , B. Andrews, G.M. Santangelo, “The global transcriptional activator of Saccharomyces cerevisiae, Gcr1p, mediates the response to glucose by stimulating protein synthesis and CLN-dependent cell cycle progression”, Genetics Vol.165, Issue.3, pp 1017–1029, 2003.
H.T.A. Jaspers, J. van Steveninck, “Transport-associated phosphorylation of 2-deoxy-d-glucose in Saccharomyces fragilis”, BBA Biomembranes, Vol.406, Issue.3, pp 370–85, 1975.
Z. Lobo, P.K. Maitra, “Resistance to 2-deoxyglucose in yeast: a direct selection of mutants lacking glucose-phosphorylating enzymes”, Mol Gen Genet, Vol.157, Issue.3, pp 297–300, 1977.
A.N. Wick, D.R. Drury, H.I. Nakada, J.B. Wolfe, “Localization of the primary metabolic block produced by 2-deoxyglucose”, J Biol Chem, Vol.224, Issue.2, pp 963–969, 1957.
W. Chen, M. Gueron, “The inhibition of bovine heart hexokinase by 2-deoxy-Dglucose-6-phosphate: Characterization by 31P NMR and metabolic implications”, Biochimie, Vol. 74, Issue.9-10, pp 867–873, 1992.
L.E. Burton, W.W. Wells, “Studies on the effect of 5-thio-d-glucose and 2-deoxy-d-glucose on myo-inositol metabolism”, Archives of Biochemistry and Biophysics, Vol.181, Issue.2, pp 384-392, 1977.
J.I. Nikawa, T. Nagumo, S. Yamashita, “myo-Inositol Transport in Saccharomyces cerevisiae”, Journal of Bacteriology, Vol.150, Issue.2 , pp 441-446, 1982.
G.M. Carman and G.S. Han, “Regulation of phospholipid synthesis in the yeast Saccharomyces cerevisiae”, Annu. Rev. Biochem, Vol.80, pp 859–883, 2011.
S.A. Henry, S.D. Kohlwein and G.M. Carman, “Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae”, Genetics. Vol.190, Issue.2, pp 317–349, 2013.
J.D. York, S. Guo, A.R. Odom, B.D. Spiegelberg and L.E. Stolz, “An expanded view of inositol signalling”, Adv. Enzyme Regul, Vol.41, pp 57–71, 2001.
N. Bachhawat, Q. Ouyang and S.A. Henry, “Functional characterization of an inositol-sensitive upstream activation sequence in yeast. A cis-regulatory element responsible for inositol choline-mediated regulation of phospholipid biosynthesis”, J. Biol. Chem, Vol.270, Issue.42, pp 25087–25095,1995.
J.R. Gibbins, “Epithelial cell motility: The effect of 2-deoxyglucose on cell migration, ATP production, and the structure of the cytoplasmic ground substance in lamellipodia of epithelial cells in culture”, Cell Motil, Vol.2, Issue.1, pp 25–46, 1982.
H.T. Kang, E.S. Hwang, “2-Deoxyglucose: An anticancer and antiviral therapeutic, but not anymore a low glucose mimetic”, Life Sci, Vol.78, Issue.12, pp 1392–1399, 2006.
M. Ralser, M.M. Wamelink, E.A. Struys, C. Joppich, S. Krobitsch, C. Jakobs, H. Lehrach, “A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growth”, Proc Natl Acad Sci U S A, Vol.105, Issue.46, pp 17807-11, 2008.
R.R. McCartney, D.G. Chandrashekarappa, B.B. Zhang, and M.C. Schmidt, “Genetic Analysis of Resistance and Sensitivity to 2-Deoxyglucose in Saccharomyces cerevisiae”, Genetics, Vol.198, Issue.2, pp 635–646, 2014.
P.A. Gibney, A. Schieler, J.C. Chen, J.M. Bacha-Hummel, M. Botstein, M. Volpe, S.J. Silverman, Y. Xu, B.D. Bennett, J.D. Rabinowitz, D. Botstein, “Common and divergent features of galactose-1-phosphate and fructose-1-phosphate toxicity in yeast”, Mol Biol Cell, Vol.29, Issue.8, pp 897-910, 2018.
M.M. Bradford, “A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding”, Anal. Biochem, Vol.72, Issue.1-2, pp 248–254, 1976.
M. Rose and D. Botstein, “Construction and use of gene fusions to lacZ (β- galactosidase) that are expressed in yeast”, Methods Enzymol, Vol.101, pp 167–180, 1983.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors contributing to this journal agree to publish their articles under the Creative Commons Attribution 4.0 International License, allowing third parties to share their work (copy, distribute, transmit) and to adapt it, under the condition that the authors are given credit and that in the event of reuse or distribution, the terms of this license are made clear.
Download Article Template
