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Your search keyword '"Kovalevska, O."' showing total 4 results
Start Over Author "Kovalevska, O." Publisher palladin institute of biochemistry, national academy of sciences of ukraine
4 results on '"Kovalevska, O."'

1. INHIBITION OF ERN1 SIGNALING ENZYME AFFECTS HYPOXIC REGULATION OF THE EXPRESSION OF E2F8, EPAS1, HOXC6, ATF3, TBX3 AND FOXF1 GENES IN U87 GLIOMA CELLS.

Author

Minchenko OH, Tsymbal DO, Minchenko DO, Kovalevska OV, Karbovskyi LL, and Bikfalvi A

Subjects
Activating Transcription Factor 3 genetics, Activating Transcription Factor 3 metabolism, Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Hypoxia genetics, Cell Line, Tumor, Cell Proliferation, Endoplasmic Reticulum Stress genetics, Endoribonucleases antagonists & inhibitors, Endoribonucleases metabolism, Forkhead Transcription Factors genetics, Forkhead Transcription Factors metabolism, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Humans, Neuroglia metabolism, Neuroglia pathology, Protein Serine-Threonine Kinases antagonists & inhibitors, Protein Serine-Threonine Kinases metabolism, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Repressor Proteins genetics, Repressor Proteins metabolism, T-Box Domain Proteins genetics, T-Box Domain Proteins metabolism, Transfection, Endoribonucleases genetics, Gene Expression Regulation, Neoplastic drug effects, Neuroglia drug effects, Oxygen pharmacology, Protein Serine-Threonine Kinases genetics, Signal Transduction drug effects
Abstract

Hypoxia as well as the endoplasmic reticulum stress are important factors of malignant tumor growth and control of the expression of genes, which regulate numerous metabolic processes and cell proliferation. Furthermore, blockade of ERN1 (endoplasmic reticulum to nucleus 1) suppresses cell proliferation and tumor growth. We studied the effect of hypoxia on the expression of genes encoding the transcription factors such as E2F8 (E2F transcription factor 8), EPAS1 (endothelial PAS domain protein 1), TBX3 (T-box 3), ATF3 (activating transcription factor 3), FOXF1 (forkhead box F), and HOXC6 (homeobox C6) in U87 glioma cells with and without ERN1 signaling enzyme function. We have established that hypoxia enhances the expression of HOXC6, E2F8, ATF3, and EPAS1 genes but does not change TBX3 and FOXF1 gene expression in glioma cells with ERNI function. At the same time, the expression level of all studied genes is strongly decreased, except for TBX3 gene, in glioma cells without ERN1 function. Moreover, the inhibition of ERN1 signaling enzyme function significantly modifies the effect of hypoxia on the expression of these transcription factor genes. removes or introduces this regulation as well as changes a direction or magnitude of hypoxic regulation. Present study demonstrates that fine-tuning of the expression of proliferation related genes depends upon hypoxia and ERN1-mediated endoplasmic reticulum stress signaling and correlates with slower proliferation rate of glioma cells without ERN1 function.

Published
2015

2. Expression of phosphoribosyl pyrophosphate synthetase genes in U87 glioma cells with ERN1 knockdown: effect of hypoxia and endoplasmic reticulum stress.

Author

Minchenko OH, Garmash IA, Kovalevska OV, Tsymbal DO, and Minchenko DO

Subjects
Cell Hypoxia, Cell Line, Tumor, Cell Proliferation drug effects, Endoplasmic Reticulum drug effects, Endoribonucleases deficiency, Gene Expression Regulation, Gene Knockdown Techniques, Humans, Isoenzymes genetics, Isoenzymes metabolism, Neuroglia drug effects, Neuroglia metabolism, Neuroglia pathology, Pentose Phosphate Pathway drug effects, Protein Serine-Threonine Kinases deficiency, Ribose-Phosphate Pyrophosphokinase metabolism, Signal Transduction, Tunicamycin pharmacology, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum Stress genetics, Endoribonucleases genetics, Oxygen pharmacology, Pentose Phosphate Pathway genetics, Protein Serine-Threonine Kinases genetics, Ribose-Phosphate Pyrophosphokinase genetics
Abstract

Activation of pentose phosphate pathway is an important factor of enhanced cell proliferation and tumor growth. Phosphoribosyl pyrophosphate synthetase (PRPS) is a key enzyme of this pathway and plays a central role in the synthesis of purines and pyrimidines. Hypoxia as well as ERN1 (from endoplasmic reticulum to nuclei-1) mediated endoplasmic reticulum stress response-signalling pathway is linked to the proliferation because the blockade of ERN1 suppresses tumor growth, including glioma. We studied the expression of different PRPS genes in glioma cells with ERN1 knockdown under hypoxic condition. It was shown that hypoxia decreases the expression of PRPS1 and PRPS2 genes in both types of glioma cells, being more pronounced in cells without ERN1 function, but PRPSAP1 and PRPSAP2 gene expressions are suppressed by hypoxia only in glioma cells with blockade of ERN1. Moreover, the blockade of endoribonuclease activity of ERN1 does not affect the expression of PRPS1 and PRPS2 as well as PPRS-associated protein genes in U87 glioma cells. At the same time, the induction of endoplasmic reticulum stress by tunicamycin in glioma cells with suppressed activity of ERN1 endoribonuclease decreases the expression level of PRPS1 and PRPS2 genes only. Results of this investigation clearly demonstrated that the expression of different genes encoding subunits of PRPS enzyme is affected by hypoxia in U87 glioma cells, but the effect of hypoxia is modified by suppression of endoplasmic reticulum stress signaling enzyme ERN1.

Published
2014

3. 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

4. Effect of hypoxia on the expression of CCN2, PLAU, PLAUR, SLURP1, PLAT and ITGB1 genes in ERN1 knockdown U87 glioma cells.

Author

Minchenko OH, Kharkova AP, Kubaichuk KI, Minchenko DO, Hlushchak NA, and Kovalevska OV

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

The endoplasmic reticulum stress is an important factor of tumor growth and is induced in cancer cells. We have studied the effect of ERN1 knockdown as well as hypoxia on the expression of genes encoding factors, which control cell proliferation, in U87 glioma cells. It was shown that the complete blockade of ERN1 enzyme function leads to an increase of the PLAT (tissue plasminogen activator), CCN2 (CCN family member 2), and ITGB1 (integrin β-1) as well as to a decrease ofPLAU (plasminogen activator, urokinase), PLAUR (plasminogen activator, urokinase receptor), and SLURP1 (secreted LY6/PLAUR domain containing 1) mRNA expressions. Moreover, we have shown that hypoxia does not affect the expression level of ITGB1 mRNA, but increases that of CCN2, PLAUR, SLURP1, and PLAT mRNA and decreases the expression level of only PLAU mRNA in control glioma cells. At the same time, in ERN1 knockdown glioma cells the expression level of PLAU PLAUR, and SLURP1 mRNA is decreased under hypoxia, but PLAT and ITGB1 mRNA expression levels are increased under these experimental conditions. Thus, results of this study have shown that the expression level of all studied genes is affected by ERN1 knockdown as well as by hypoxia and that the effect of hypoxia mostly depends on ERN1 signaling enzyme function.

Published
2014

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