GLUCOSE AND GLUTAMINE DEPRIVATIONS AFFECT THE EXPRESSION OF MAP3K5, MAP4K3, CIB1, RIPK1, AND RIPK2 GENES IN U87 GLIOMA CELLS WITH BLOCKADE OF ERN1 SIGNALING ENZYME FUNCTION
Journal Title: Naukovyi visnyk Chernivetskoho universytetu. Biolohiia (Biolohichni systemy) - Year 2014, Vol 6, Issue 2
Abstract
Protein kinases play an important role in malignant tumor growth as key regulators of different metabolic processes. We studied the effect of glucose and glutamine deprivation conditions on the expression level of mitogen-activated protein kinase kinase kinase kinase 3 (MAP4K3), mitogen-activated protein kinase kinase kinase 5 (MAP3K5), receptor (TNFRSF)-interacting serine-threonine kinase 1 (RIPK1), and RIPK2 as well as protein kinase interacting protein CIB1 mRNA in U87 glioma cells. It was shown that the suppression of both enzymatic activities of sensor and signaling enzyme ERN1 (endoplasmic reticulum to nucleus signaling 1), the major component of endoplasmic reticulum stress signaling, decreases the expression level of genes encoding MAP4K3, RIPK2, and CIB1 in U87 glioma cells, but increases – RIPK1 gene expression. At the same time, no significant changes were observed in MAP3K5 gene expression in glioma cells with blockade of ERN1 signaling enzyme. Glutamine deprivation condition leads to increase the expression level of RIPK1 gene and to decrease – CIB1 gene in control glioma cells, but ERN1 knockdown modifies the effect of glutamine deprivation on the expression most of these genes. It was also shown that the expression level of MAP3K5, RIPK1, RIPK2, and CIB1 genes did not change significantly in control glioma cells at glucose deprivation condition, but in cells with ERN1 knockdown glucose deprivation enhances the expression of RIPK1 and RIPK2 genes. Thus, suppression of ERN1 enzyme function also changes the effect of glucose deprivation on the expression of most studied genes in glioma cells. Results of this investigation clearly demonstrated that the expression of MAP4K3, RIPK1, RIPK2, and CIB1genes in U87 glioma cells is dependent from blockade of ERN1-mediated endoplasmic reticulum stress and is mostly regulated by glutamine and glucose deprivation in dependence from ERN1 signaling enzyme function.
Authors and Affiliations
T. V. BAKALETS, D. O. MINCHENKO, O. O. RATUSHNA, O. Riabovol, О. H. MINCHENKO
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