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IRE1 inhibition affects the expression of insulin-like growth factor binding protein genes and modifies its sensitivity to glucose deprivation in U87 glioma cells.
Endocr Regul. 2015 Oct; 49(4):185-97.ER

Abstract

OBJECTIVE

The aim of the present study was to investigate the effect of inhibition of endoplasmic reticulum stress signaling mediated by IRE1/ERN1 (inositol-requiring enzyme 1/endoplasmic reticulum to nucleus signaling 1) on the expression of genes encoding different groups of insulin-like growth binding proteins (IGFBP6 and IGFBP7) and CCN family (IGFBP8/CTGF/CCN2, IGFBP9/NOV/CCN3, IGFBP10/CYR61/CCN1, WISP1/CCN4, and WISP2/CCN5) and its sensitivity to glucose deprivation in U87 glioma cells.

METHODS

The expression of IGFBP6, IGFBP7, IGFBP8, IGFBP9, IGFBP10, WISP1, and WISP2 genes was studied by qPCR in control U87 glioma cells (wild-type) and its subline with IRE1 signaling enzyme loss of function upon glucose deprivation.

RESULTS

The expression of IGFBP8, IGFBP9, and WISP2 genes was up-regulated in control glioma cells upon glucose deprivation with most significant changes for IGFBP9 gene. At the same time, the expression of IGFBP6, IGFBP10, and WISP1 genes was resistant to glucose deprivation in these glioma cells, but the IGFBP7 gene expression was down-regulated. The inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 in glioma cells modified the sensitivity of most studied gene expressions to glucose deprivation condition: introduced sensitivity of IGFBP10 and WISP1 genes to glucose deprivation, enhanced the effect of this deprivation on IGFBP7 and IGFBP9 gene expressions, and reduced this effect on WISP2 gene and induced suppressive effect of glucose deprivation on the expression of IGFBP8 gene. Furthermore, the inhibition of IRE1 strongly affected the expression of all studied genes in glioma cells upon regular growing condition in gene specific manner: up-regulated the expression levels of IGFBP7, IGFBP8, IGFBP10, WISP1, and WISP2 genes and down-regulated the IGFBP6 and IGFBP9 genes.

CONCLUSIONS

The data of this investigation demonstrate that the expression of IGFBP7, IGFBP8, IGFBP9, and WISP2 genes are sensitive to glucose deprivation in U87 glioma cells and that inhibition of IRE1 signaling enzyme function may significantly affect the expression of all studied genes in the presence of glucose as well as modify the effect of glucose deprivation on the expression of most studied genes. These data also show that proteins encoded by these genes may participate in the regulation of metabolic and proliferative processes via IGF/INS receptors and possibly other signaling pathways as well, via IRE1 signaling, which is a central mediator of the unfolded protein response and an important component of the tumor growth and metabolic diseases.

Authors

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Pub Type(s)

Journal Article

Language

eng

PubMed ID

26494037

Citation

Minchenko, D O., et al. "IRE1 Inhibition Affects the Expression of Insulin-like Growth Factor Binding Protein Genes and Modifies Its Sensitivity to Glucose Deprivation in U87 Glioma Cells." Endocrine Regulations, vol. 49, no. 4, 2015, pp. 185-97.
Minchenko DO, Kharkova AP, Tsymbal DO, et al. IRE1 inhibition affects the expression of insulin-like growth factor binding protein genes and modifies its sensitivity to glucose deprivation in U87 glioma cells. Endocr Regul. 2015;49(4):185-97.
Minchenko, D. O., Kharkova, A. P., Tsymbal, D. O., Karbovskyi, L. L., & Minchenko, O. H. (2015). IRE1 inhibition affects the expression of insulin-like growth factor binding protein genes and modifies its sensitivity to glucose deprivation in U87 glioma cells. Endocrine Regulations, 49(4), 185-97.
Minchenko DO, et al. IRE1 Inhibition Affects the Expression of Insulin-like Growth Factor Binding Protein Genes and Modifies Its Sensitivity to Glucose Deprivation in U87 Glioma Cells. Endocr Regul. 2015;49(4):185-97. PubMed PMID: 26494037.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IRE1 inhibition affects the expression of insulin-like growth factor binding protein genes and modifies its sensitivity to glucose deprivation in U87 glioma cells. AU - Minchenko,D O, AU - Kharkova,A P, AU - Tsymbal,D O, AU - Karbovskyi,L L, AU - Minchenko,O H, PY - 2015/10/24/entrez PY - 2015/10/27/pubmed PY - 2016/7/2/medline KW - IGFBP10 KW - IGFBP6 KW - IGFBP7 KW - IGFBP8 KW - IGFBP9 KW - IRE1 inhibition KW - U87 glioma cells KW - WISP1 KW - WISP2 KW - glucose deprivation. KW - mRNA expression SP - 185 EP - 97 JF - Endocrine regulations JO - Endocr Regul VL - 49 IS - 4 N2 - OBJECTIVE: The aim of the present study was to investigate the effect of inhibition of endoplasmic reticulum stress signaling mediated by IRE1/ERN1 (inositol-requiring enzyme 1/endoplasmic reticulum to nucleus signaling 1) on the expression of genes encoding different groups of insulin-like growth binding proteins (IGFBP6 and IGFBP7) and CCN family (IGFBP8/CTGF/CCN2, IGFBP9/NOV/CCN3, IGFBP10/CYR61/CCN1, WISP1/CCN4, and WISP2/CCN5) and its sensitivity to glucose deprivation in U87 glioma cells. METHODS: The expression of IGFBP6, IGFBP7, IGFBP8, IGFBP9, IGFBP10, WISP1, and WISP2 genes was studied by qPCR in control U87 glioma cells (wild-type) and its subline with IRE1 signaling enzyme loss of function upon glucose deprivation. RESULTS: The expression of IGFBP8, IGFBP9, and WISP2 genes was up-regulated in control glioma cells upon glucose deprivation with most significant changes for IGFBP9 gene. At the same time, the expression of IGFBP6, IGFBP10, and WISP1 genes was resistant to glucose deprivation in these glioma cells, but the IGFBP7 gene expression was down-regulated. The inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 in glioma cells modified the sensitivity of most studied gene expressions to glucose deprivation condition: introduced sensitivity of IGFBP10 and WISP1 genes to glucose deprivation, enhanced the effect of this deprivation on IGFBP7 and IGFBP9 gene expressions, and reduced this effect on WISP2 gene and induced suppressive effect of glucose deprivation on the expression of IGFBP8 gene. Furthermore, the inhibition of IRE1 strongly affected the expression of all studied genes in glioma cells upon regular growing condition in gene specific manner: up-regulated the expression levels of IGFBP7, IGFBP8, IGFBP10, WISP1, and WISP2 genes and down-regulated the IGFBP6 and IGFBP9 genes. CONCLUSIONS: The data of this investigation demonstrate that the expression of IGFBP7, IGFBP8, IGFBP9, and WISP2 genes are sensitive to glucose deprivation in U87 glioma cells and that inhibition of IRE1 signaling enzyme function may significantly affect the expression of all studied genes in the presence of glucose as well as modify the effect of glucose deprivation on the expression of most studied genes. These data also show that proteins encoded by these genes may participate in the regulation of metabolic and proliferative processes via IGF/INS receptors and possibly other signaling pathways as well, via IRE1 signaling, which is a central mediator of the unfolded protein response and an important component of the tumor growth and metabolic diseases. SN - 1210-0668 UR - https://www.unboundmedicine.com/medline/citation/26494037/IRE1_inhibition_affects_the_expression_of_insulin_like_growth_factor_binding_protein_genes_and_modifies_its_sensitivity_to_glucose_deprivation_in_U87_glioma_cells_ L2 - http://www.aepress.sk/_downloads/dl.php?from=pubmed&journal=ER&file=2015_04_185.pdf DB - PRIME DP - Unbound Medicine ER -