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Your search keyword '"Danilovskyi SV"' showing total 2 results
Start Over Author "Danilovskyi SV" Publisher palladin institute of biochemistry, national academy of sciences of ukraine
2 results on '"Danilovskyi SV"'

1. Inhibition of IRE1 modifies the hypoxic regulation of GADD family gene expressions in U87 glioma cells.

Author

Minchenko OH, Kryvdiuk IV, Riabovol OO, Minchenko DO, Danilovskyi SV, and Ratushna OO

Subjects
Antigens, Differentiation genetics, Antigens, Differentiation metabolism, Apoptosis genetics, Apoptosis Inducing Factor genetics, Apoptosis Inducing Factor metabolism, Cell Cycle Proteins metabolism, Cell Hypoxia, Cell Line, Tumor, Cell Proliferation, Endoribonucleases deficiency, Gene Knockdown Techniques, Humans, Neuroglia pathology, Nuclear Proteins metabolism, Plasmids chemistry, Plasmids metabolism, Protein Phosphatase 1 metabolism, Protein Serine-Threonine Kinases deficiency, Signal Transduction, Transcription Factor CHOP genetics, Transcription Factor CHOP metabolism, Transfection, eIF-2 Kinase genetics, eIF-2 Kinase metabolism, Cell Cycle Proteins genetics, Endoplasmic Reticulum Stress genetics, Endoribonucleases genetics, Gene Expression Regulation, Neoplastic, Neuroglia metabolism, Nuclear Proteins genetics, Protein Phosphatase 1 genetics, Protein Serine-Threonine Kinases genetics
Abstract

We have studied hypoxic regulation of the expression of genes encoded GADD (growth arrest and DNA damage) family proteins in U87 glioma cells in relation to inhibition of IRE1 (inositol requiring enzyme-1), which controls cell proliferation and tumor growth as a central mediator of endoplasmic reticulum stress. We have shown that hypoxia up-regulates the expression of GADD34, GADD45A, GADD45B, and GADD153 genes, which are related to cell proliferation and apoptosis, in control (transfected by empty vector) glioma cells in gene specific manner. At the same time, the expression level of EIF2AK 1 (eukaryotic translation initiation factor 2-alpha kinase 1) and AI FM1 (apoptosis inducing factor, mitochondria associated 1) genes in these cells is down-regulated upon hypoxic condition. It was also shown that inhibition of ІRE1 signaling enzyme function in U87 glioma cells enhances the effect of hypoxia on these genes expression, except EIF2AK 1 and AI FM1 genes. Furthermore, the expression of all studied genes in ІRE1 knockdown cells is significantly decreased upon normoxic condition, except GADD45B gene, which expression level is strongly up-regulated. Therefore, the expression level of genes encoding GADD34, GADD45A, GADD45B, GADD153, EIF2AK 1, and AI FM1 is affected by hypoxia and by inhibition of IRE1-mediated endoplasmic reticulum stress signaling in gene specific manner and correlates with suppression of glioma cell proliferation upon inhibition of the IRE1 enzyme function.

Published
2016
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2. ERN1 knockdown modifies the hypoxic regulation of TP53, MDM2, USP7 and PERP gene expressions in U87 glioma cells.

Author

Danilovskyi SV, Minchenko DO, Moliavko OS, Kovalevska OV, Karbovskyi LL, and Minchenko OH

Subjects
Apoptosis genetics, Cell Hypoxia genetics, Cell Line, Tumor, Gene Knockdown Techniques, Humans, Cell Proliferation genetics, Endoplasmic Reticulum Stress genetics, Endoribonucleases genetics, Gene Expression Regulation, Protein Serine-Threonine Kinases genetics
Abstract

Endoplasmic reticulum stress and hypoxia are necessary components of malignant tumors growth and suppression of ERN1 (from endoplasmic reticulum to nuclei-1) signalling pathway, which is linked to the apoptosis and cell death processes, significantly decreases proliferative processes. Glioma cells with ERN1 knockdown were used in order to investigate the effect of ERNI blockade on the expression of TP53, MDM2, PERP, and USP7 genes and its hypoxic regulation. We have studied the expression of TP53 (tumor protein 53), MDM2 (TP53 E3 ubiquitin protein ligase homolog), PERP (TP53 apoptosis effector), and USP7 (ubiquitin specific peptidase 7) genes, which are related to cell proliferation and apoptosis, in glioma cells with ERN1 knockdown under hypoxic condition. It was shown that blockade of ERNI gene function in U87 glioma cells intensified the expression of TP53 and USP7 genes, but decreased the expression ofMDM2 and PERP genes. Thus, an enhanced expression of TP53 gene in ERN1 knockdown glioma cells correlates with the decreased level of ubiquitin ligase MDM2 and increased expression level of USP7 which deubiquitinates TP53 and MDM2 and induces TP53-dependent cell growth repression and apoptosis. At the same time, the expression levels of TP53, MDM2, and USP7 genes do not change significantly in glioma cells with suppression of endoribonuclease activity only, but PERP gene expression is strongly increased. Moreover, the expression of TP53 and UPS7 genes is decreased in hypoxic conditions in control glioma cells only; however, MDM2 and PERP gene expressions are increased in both cell types, being more significant in ERN1 knockdown cells. Thus, the expression of genes encoding TP53 and related to TP53 factors depends upon the endoplasmic reticulum stress signaling as well as on hypoxia, and correlates with suppression of glioma growth under ERN1 knockdown.

Published
2014

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