<abstract xmlns="http://www.w3.org/1999/xhtml"><bold>Objective.</bold> The aim of the present study was to examine the effect of glucose deprivation on the expression of genes encoded glucocorticoid receptor (NR3C1) and some related proteins (NR3C2, AHR, NRIP1, NNT, ARHGAP35, SGK1, and SGK3) in U87 glioma cells in response to inhibition of endoplasmic reticulum stress signaling mediated by ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1/inositol requiring enzyme 1) for evaluation of their possible significance in the control of glioma growth through endoplasmic reticulum stress signaling mediated by IRE1 and glucose deprivation.<bold>Methods.</bold> The expression of <italic>NR3C1</italic>, <italic>NR3C2</italic>, <italic>AHR</italic>, <italic>NRIP1</italic>, <italic>NNT</italic>, <italic>ARHGAP35</italic>, <italic>SGK1</italic>, and <italic>SGK3</italic> genes in U87 glioma cells transfected by empty vector pcDNA3.1 (control cells) and cells without ERN1 signaling enzyme function (transfected by dnERN1) under glucose deprivation was studied by real time quantitative polymerase chain reaction.<bold>Results.</bold> It was shown that the expression level of <italic>NR3C2</italic>, <italic>AHR</italic>, <italic>SGK1</italic>, <italic>SGK3</italic>, and <italic>NNT</italic> genes was up-regulated in control U87 glioma cells under glucose deprivation condition in comparison with the control cells growing with glucose. At the same time, the expression of <italic>NRIP1</italic> gene is down-regulated in these glioma cells under glucose deprivation, but <italic>NR3C1</italic> and <italic>ARHGAP35</italic> genes was resistant to this experimental condition. We also showed that inhibition of ERN1 signaling enzyme function significantly modified the response of most studied gene expressions to glucose deprivation condition. Thus, effect of glucose deprivation on the expression level of <italic>NR3C2</italic>, <italic>AHR</italic>, and <italic>SGK1</italic> genes was significantly stronger in ERN1 knockdown U87 glioma cells since the expression of <italic>NNT</italic> gene was resistant to glucose deprivation condition. Moreover, the inhibition of ERN1 enzymatic activities in U87 glioma cells led to up-regulation of ARHGAP35 gene expression and significant down-regulation of the expression of <italic>SGK3</italic> gene in response to glucose deprivation condition.<bold>Conclusions.</bold> Results of this study demonstrated that glucose deprivation did not change the expression level of <italic>NR3C1</italic> gene but it significantly affected the expression of <italic>NR3C2</italic>, <italic>AHR</italic>, <italic>NRIP</italic>, <italic>SGK1</italic>, <italic>SGK3</italic>, and <italic>NNT</italic> genes in vector-transfected U87 glioma cells in gene specific manner and possibly contributed to the control of glioma growth since the expression of most studied genes in glucose deprivation condition was significantly dependent on the functional activity of IRE1 signaling enzyme.</abstract>

Objective. The aim of the present study was to examine the effect of glucose deprivation on the expression of genes encoded glucocorticoid receptor (NR3C1) and some related proteins (NR3C2, AHR, NRIP1, NNT, ARHGAP35, SGK1, and SGK3) in U87 glioma cells in response to inhibition of endoplasmic reticulum stress signaling mediated by ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1/inositol requiring enzyme 1) for evaluation of their possible significance in the control of glioma growth through endoplasmic reticulum stress signaling mediated by IRE1 and glucose deprivation.Methods. The expression of NR3C1, NR3C2, AHR, NRIP1, NNT, ARHGAP35, SGK1, and SGK3 genes in U87 glioma cells transfected by empty vector pcDNA3.1 (control cells) and cells without ERN1 signaling enzyme function (transfected by dnERN1) under glucose deprivation was studied by real time quantitative polymerase chain reaction.Results. It was shown that the expression level of NR3C2, AHR, SGK1, SGK3, and NNT genes was up-regulated in control U87 glioma cells under glucose deprivation condition in comparison with the control cells growing with glucose. At the same time, the expression of NRIP1 gene is down-regulated in these glioma cells under glucose deprivation, but NR3C1 and ARHGAP35 genes was resistant to this experimental condition. We also showed that inhibition of ERN1 signaling enzyme function significantly modified the response of most studied gene expressions to glucose deprivation condition. Thus, effect of glucose deprivation on the expression level of NR3C2, AHR, and SGK1 genes was significantly stronger in ERN1 knockdown U87 glioma cells since the expression of NNT gene was resistant to glucose deprivation condition. Moreover, the inhibition of ERN1 enzymatic activities in U87 glioma cells led to up-regulation of ARHGAP35 gene expression and significant down-regulation of the expression of SGK3 gene in response to glucose deprivation condition.Conclusions. Results of this study demonstrated that glucose deprivation did not change the expression level of NR3C1 gene but it significantly affected the expression of NR3C2, AHR, NRIP, SGK1, SGK3, and NNT genes in vector-transfected U87 glioma cells in gene specific manner and possibly contributed to the control of glioma growth since the expression of most studied genes in glucose deprivation condition was significantly dependent on the functional activity of IRE1 signaling enzyme.

Effect of glucose deprivation on the expression of genes encoding glucocorticoid receptor and some related factors in ERN1-knockdown U87 glioma cells

Department of Molecular Biology, Palladin Institute of Biochemistry

Endocrine Regulations

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Objective. The aim of the present study was to examine the effect of glucose deprivation on the expression of genes encoded glucocorticoid receptor (NR3C1) and...

Effect of glucose deprivation on the expression of genes encoding glucocorticoid receptor and some related factors in ERN1-knockdown U87 glioma cells

Online veröffentlicht: 15. Nov. 2019

Seitenbereich: 237 - 249

DOI: https://doi.org/10.2478/enr-2019-0024

Schlüsselwörter
glucose deprivation, mRNA expression, NR3C1, NR3C2, AHR, NRIP1, SGK1, SGK3, ARHGAP35, NNT, ERN1 inhibition, U87 glioma cells

© 2019 Olena O. Riabovol et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Effect of glucose deprivation on the expression of genes encoding glucocorticoid receptor and some related factors in ERN1-knockdown U87 glioma cells

Online veröffentlicht: 15. Nov. 2019

Seitenbereich: 237 - 249

DOI: https://doi.org/10.2478/enr-2019-0024

Schlüsselwörterglucose deprivation, mRNA expression, NR3C1, NR3C2, AHR, NRIP1, SGK1, SGK3, ARHGAP35, NNT, ERN1 inhibition, U87 glioma cells

© 2019 Olena O. Riabovol et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Schlüsselwörter
glucose deprivation, mRNA expression, NR3C1, NR3C2, AHR, NRIP1, SGK1, SGK3, ARHGAP35, NNT, ERN1 inhibition, U87 glioma cells