ISSN 2410-7751 (Print)
ISSN 2410-776X (on-line)
"Biotechnologia Acta" V. 9, No 2, 2016
https://doi.org/10.15407/biotech9.02.037
Р. 37-47, Bibliography 43, English
Universal Decimal Classification: 577.112:616
O. O. Riabovol 1, D. O. Tsymbal 1, D. O. Minchenko 1, 2, O.O. Ratushna 1, O. H. Minchenko 1
1 Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv
2 Bohomolets National Medical University, Kyiv
We have studied the glucose and glutamine deprivation effect on the expression of nuclear genes encoding mitochondrial proteins in U87 glioma cells in relation to inhibition of inositol requiring enzyme-1 (IRE1). It was shown that glutamine deprivation down-regulated the expression of mitochondrial (NADP+)-dependent isocitrate dehydrogenase 2 (IDH2), malic enzyme 2 (ME2), mitochondrial aspartate aminotransferase (GOT2), and subunit B of succinate dehydrogenase (SDHB) genes in control glioma cells in gene specific manner. At the same time, the expression level of malate dehydrogenase 2 (MDH2) and subunit D of succinate dehydrogenase (SDHD) genes in these cells was not changed upon glutamine deprivation. It was also shown that inhibition of ІRE1 signaling enzyme function in U87 glioma cells modified the glutamine deprivation effect on the expression of all studied genes. Furthermore, the expression of the majority of studied genes was resistant to glucose deprivation, except IDH2 and SDHB genes, which expression levels were slightly down-regulated. Inhibition of IRE1 modified the effect of glucose deprivation on ME2, SDHB, SDHD, and GOT2 genes expression. Therefore, glucose and glutamine deprivation affected the expression level of the majority of nuclear genes encoding mitochondrial proteins in relation to the functional activity of IRE1 enzyme, which is a central mediator of endoplasmic reticulum stress and controls cell proliferation and tumor growth.
Key words: glucose and glutamine deprivations, mitochondrial proteins, IRE1 inhibition, U87 glioma cells.
© Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, 2016
References
1. Cobanoglu B., Ceyran A. B., Simsek M., ?enol S. Immunohistochemical analysis of Bax and AIF in colorectal tumors. Int. J. Clin. Exp. Med. 2015, 8 (9), 16071?16076.
2. Lee W., St John J. The control of mitochondrial DNA replication during development and tumorigenesis. Ann. N. Y. Acad. Sci. 2015, V. 1350, P. 95?106. http://dx.doi.org/10.1111/nyas.12873.
3. Lo Y. W., Lin S. T., Chang S. J., Chan C. H., Lyu K. W., Chang J. F., May E. W., Lin D. Y., Chou H. C., Chan H. L. Mitochondrial proteomics with siRNA knockdown to reveal ACAT1 and MDH2 in the development of doxorubicin-resistant uterine cancer. J. Cell. Mol. Med. 2015, 719 (4), 744?759. http://dx.doi.org/10.1111/jcmm.12388
4. Zhao H., Wang C., Lu B., Zhou Z., Jin Y., Wang Z., Zheng L., Liu K., Luo T., Zhu D., Chi G., Luo Y., Ge P. Pristimerin triggers AIF-dependent programmed necrosis in glioma cells via activation of JNK. Cancer Lett. 2016, 374 (1), 136?148. http://dx.doi.org/10.1016/j.canlet.2016.01.055
5. Swan E. J., Maxwell A. P., McKnight A. J. Distinct methylation patterns in genes that affect mitochondrial function are associated with kidney disease in blood-derived DNA from individuals with type 1 diabetes. Diabet. Med. 2015, 32 (8), 1110?1115.
http://dx.doi.org/10.1111/dme.12775
6. Minchenko O. H., Tsymbal D. O., Minchenko D. O., Riabovol O. O., Ratushna O. O. Hypoxic regulation of the expressions of proliferation related genes in U87 glioma cells upon inhibition of IRE1 signaling. Ukr. Biochem. J. 2016, 88 (1), 11?21. doi.org/10.15407/j.bj88.01.011.
7. Linkowska K., Jawie? A., Marsza?ek A., Malyarchuk B. A., To?ska K., Bartnik E., Skonieczna K., Grzybowski T. Mitochondrial DNA polymerase ? mutations and their implications in mtDNA alterations in colorectal cancer. Ann. Hum. Genet. 2015, Apr 7. http://dx.doi.org/10.1111/ahg.12111
8. Lenihan C. R., Taylor C. T. The impact of hypoxia on cell death pathways. Biochem. Soc. Trans. 2013, V. 41, P. 657–663. http://dx.doi.org/10.1042/BST20120345
9. Minchenko O. H., Kryvdiuk I. V., Riabovol O. O., Minchenko D. O., Danilovskyi S. V., Ratushna O. O. Inhibition of IRE1 modifies the hypoxic regulation of GADD family gene expressions in U87 glioma cells. Ukr. Biochem. J. 2016, 88 (2), 25?34. doi.org/10.15407/j.bj88.02.025.
10. Tsymbal D. O., Minchenko D. O., Riabovol O. O., Ratushna O. O., Minchenko O. H. IRE1 knockdown modifies glucose and glutamine deprivation effects on the expression of proliferation related genes in U87 glioma cells. Biotechnol. Acta. 2016, 9 (1), 26?37. http://dx.doi.org/10.15407/biotech8.06.009
11. Zhang X., Bian X., Kong J. The proapoptotic protein BNIP3 interacts with VDAC to induce mitochondrial release of endonuclease G. PLoS One. 2014, 9 (12), e113642. http://dx.doi.org/10.1371/journal.pone.0113642
12. Zhdanov D. D., Fahmi T., Wang X., Apostolov E. O., Sokolov N. N., Javadov S., Basnakian A. G. Regulation of apoptotic endonucleases by EndoG. DNA Cell Biol. 2015, 34 (5), 316?326. http://dx.doi.org/10.1089/dna.2014.2772
13. Hetz C., Chevet E., Harding H. P. Targeting the unfolded protein response in disease. Nat. Rev. Drug Discov. 2013, 12 (9), 703?719. http://dx.doi.org/10.1038/nrd3976
14. Mani? S. N., Lebeau J., Chevet E. Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 3. Orchestrating the unfolded protein response in oncogenesis: an update. Am. J. Physiol. Cell Physiol. 2014, 307 (10), C901?C907. http://dx.doi.org/10.1152/ajpcell.00292.2014
15. Auf G., Jabouille A., Guerit S., Pineau R., Delugin M., Bouchecareilh M., Favereaux A., Maitre M., Gaiser T., von Deimling A., Czabanka M., Vajkoczy P., Chevet E., Bikfalvi A. Moenner M. A shift from an angiogenic to invasive phenotype induced in malignant glioma by inhibition of the unfolded protein response sensor IRE1. Proc. Natl. Acad. Sci. USA. 2010, 107 (35), 15553–15558. http://dx.doi.org/10.1073/pnas.0914072107
16. Auf G., Jabouille A., Delugin M., Gu?rit S., Pineau R., North S., Platonova N., Maitre M., Favereaux A., Vajkoczy P., Seno M., Bikfalvi A., Minchenko D., Minchenko O., Moenner M. High epiregulin expression in human U87 glioma cells relies on IRE1alpha and promotes autocrine growth through EGF receptor. BMC Cancer. 2013, V. 13, P. 597. http://dx.doi.org/10.1186/1471-2407-13-597
17. Ren J. G., Seth P., Everett P., Clish C. B., Sukhatme V. P. Induction of erythroid differentiation in human erythroleukemia cells by depletion of malic enzyme 2. PLoS ONE. 2010, 5 (9), e12520. http://dx.doi.org/10.1371/journal.pone.0012520
18. Jiang P., Du W., Mancuso A., Wellen K. E., Yang X. Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature. 2013, V. 493, P. 689?693. http://dx.doi.org/10.1038/nature11776
19. Ren J. G., Seth P., Clish C. B., Lorkiewicz P. K., Higashi R. M., Lane A. N., Fan T. W., Sukhatme V. P. Knockdown of malic enzyme 2 suppresses lung tumor growth, induces differentiation and impacts PI3K/AKT signaling. Sci. Rep. 2014, V. 4, P. 5414. http://dx.doi.org/10.1038/srep05414
20. Hsieh J. Y., Li S. Y., Tsai W. C., Liu J. H., Lin C. L., Liu G. Y., Hung H. C. A small-molecule inhibitor suppresses the tumor-associated mitochondrial NAD(P)+-dependent malic enzyme (ME2) and induces cellular senescence. Oncotarget. 2015, 6 (24), 20084?20098. http://dx.doi.org/10.18632/oncotarget.3907
21. Yang H., Zhou L., Shi Q., Zhao Y., Lin H., Zhang M., Zhao S., Yang Y., Ling Z. Q., Guan K. L., Xiong Y., Ye D. SIRT3-dependent GOT2 acetylation status affects the malate-aspartate NADH shuttle activity and pancreatic tumor growth. EMBO J. 2015, 34 (8), 1110?1125. http://dx.doi.org/10.18632/oncotarget.3907
22. Eleftheriadis T., Pissas G., Antoniadi G., Liakopoulos V., Stefanidis I. Malate dehydrogenase-2 inhibitor LW6 promotes metabolic adaptations and reduces proliferation and apoptosis in activated human T-cells. Exp. Ther. Med. 2015, 10 (5), 1959?1966. http://dx.doi.org/10.3892/etm.2015.2763
23. Agaimy A. Succinate dehydrogenase (SDH)-deficient renal cell carcinoma. Pathology. 2016, 37 (2), 144?152. http://dx.doi.org/10.1007/s00292-016-0158-8
24. Miettinen M. Succinate dehydrogenase-deficient tumors--a novel mechanism of tumor formation. Duodecim. 2015, 131 (22), 2149?2156.
25. Scholz S. L., Horn S., Murali R., M?ller I., Sucker A., Sondermann W., Stiller M., Schilling B., Livingstone E., Zimmer L., Reis H., Metz C. H., Zeschnigk M., Paschen A., Steuhl K. P., Schadendorf D., Westekemper H., Griewank K.G. Analysis of SDHD promoter mutations in various types of melanoma. Oncotarget. 2015, 6 (28), 25868?25882. http://dx.doi.org/10.18632/oncotarget.4665
26. Saxena N., Maio N., Crooks D. R., Ricketts C. J., Yang Y., Wei M. H., Fan T. W., Lane A. N., Sourbier C., Singh A., Killian J. K., Meltzer P. S., Vocke C. D., Rouault T. A., Linehan W. M. SDHB-Deficient Cancers: The Role of Mutations That Impair Iron Sulfur Cluster Delivery. J. Natl. Cancer Inst. 2016, 108 (1), 287. http://dx.doi.org/10.1093/jnci/djv287
27. Viswanath P., Chaumeil M. M., Ronen S. M. Molecular Imaging of Metabolic Reprograming in Mutant IDH Cells. Front. Oncol. 2016, V. 6, P. 60. http://dx.doi.org/10.3389/fonc.2016.00060
28. Flavahan W. A., Drier Y., Liau B. B., Gillespie S. M., Venteicher A. S., Stemmer-Rachamimov A. O., Suv? M. L., Bernstein B. E. Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature. 2016, 529 (7584), 110?114. http://dx.doi.org/10.1038/nature16490
29. Park J. B., Nagar H., Choi S., Jung S. B., Kim H. W., Kang S. K., Lee J. W., Lee J. H., Park J. W., Irani K., Jeon B. H., Song H. J., Kim C. S. IDH2 deficiency impairs mitochondrial function in endothelial cells and endothelium-dependent vasomotor function. Free Rad. Biol. Med. 2016, V. 94, P. 36?46. http://dx.doi.org/10.1016/j.freeradbiomed.2016.02.017
30. Wise D. R., DeBerardinis R. J., Mancuso A., Sayed N., Zhang X.-Y., Pfeiffer H. K., Nissim I., Daikhin E., Yudkoff M., McMahon S. B., Thompson C. B. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc. Natl. Acad. Sci. USA. 2008, V. 105, P. 18782–18787. http://dx.doi.org/10.1073/pnas.0810199105
31. Fogal V., Babic I., Chao Y., Pastorino S., Mukthavaram R., Jiang P., Cho Y.-J., Pingle S. C., Crawford J. R., Piccioni D. E., Kesari S. Mitochondrial p32 is upregulated in Myc expressing brain cancers and mediates glutamine addiction. Oncotarget. 2015, V. 6, P. 1157–1170. http://dx.doi.org/10.18632/oncotarget.2708
32. Colombo S. L., Palacios-Callender M., Frakich N., Carcamo S., Kovacs I., Tudzarova S., Moncada S. Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells. Proc. Natl. Acad. Sci .USA. 2011, 108 (52), 21069?21074. http://dx.doi.org/10.1073/pnas
33. Krall A. S., Christofk H. R. Rethinking glutamine addiction. Nat. Cell. Biol. 2015, 17 (12), 1515?1517. http://dx.doi.org/10.1038/ncb3278
34. Tardito S., Oudin A., Shafiq U. Ahmed, Fack F., Keunen O., Zheng L., Miletic H., Sakariassen P. ?., Weinstock A., Wagner A., Lindsay S. L., Hock A. K., Barnett S. C., Ruppin E., M?rkve S. H., Lund-Johansen M., Chalmers A. J., Bjerkvig R., Niclou S. P., Gottlieb E. Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma. Nat. Cell. Biol. 2015, 17 (12), 1556?1568. http://dx.doi.org/10.1038/ncb3272
35. Huber A. L., Lebeau J., Guillaumot P., P?trilli V., Malek M., Chilloux J., Fauvet F., Payen L., Kfoury A., Renno T., Chevet E., Mani? S. N. p58(IPK)-mediated attenuation of the proapoptotic PERK-CHOP pathway allows malignant progression upon low glucose. Mol. Cell. 2013, 49 (6), 1049?1059. http://dx.doi.org/10.1016/j.molcel.2013.01.009
36. Zhang J., Wang G., Mao Q., Li S., Xiong W., Lin Y., Ge J. Glutamate dehydrogenase (GDH) regulates bioenergetics and redox homeostasis in human glioma. Oncotarget. 2014. Feb 24. http://dx.doi.org/10.18632/oncotarget.7657
37. Minchenko D. О., Kubajchuk К. І., Ratushna O. O., Komisarenko S. V., Minchenko O. H. The effect of hypoxia and ischemic condition on the expression of VEGF genes in glioma U87 cells is dependent from ERN1 knockdown. Adv. Biol. Chem. 2012, 2 (2), 198?206. http://dx.doi.org/10.4236/abc.2012.22024
38. Minchenko D. O., Danilovskyi S. V., Kryvdiuk I. V., Bakalets T. V., Lypova N. M., Karbovsky L. L., Minchenko O. H. Inhibition of ERN1 modifies the hypoxic regulation of the expression of TP53-related genes in U87 glioma cells. Endoplasm. Reticul. Stress Dis. 2014, 1 (1), 18?26. http://dx.doi.org/10.2478/ersc-2014-0001
39. Minchenko O. H., Opentanova I. L., Minchenko D. O., Ogura T., Esumi H. Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 gene via hypoxia-inducible factor-1alpha activation. FEBS Lett. 2004, 576 (1?2), 14?20. http://dx.doi.org/10.1016/j.febslet.2004.08.053
40. Bochkov V. N., Philippova M., Oskolkova O., Kadl A., Furnkranz A., Karabeg E., Breuss J., Minchenko O. H., Mechtcheriakova D., Hohensinner P., Rychli K., Wojta J., Resink T., Binder B. R., Leitinger N. Oxidized phospholipids stimulate angiogenesis via induction of VEGF, IL-8, COX-2 and ADAMTS-1 metalloprotease, implicating a novel role for lipid oxidation in progression and destabilization of atherosclerotic lesions. Circ. Res. 2006, 99 (8), 900?908. http://dx.doi.org/10.1161/01.RES.0000245485.04489.ee
41. Minchenko D. О., Karbovskyi L. L., Danilovskyi S. V., Moenner M., Minchenko O. H. Effect of hypoxia and glutamine or glucose deprivation on the expression of retinoblastoma and retinoblastoma-related genes in ERN1 knockdown glioma U87 cell line. Am. J. Mol. Biol. 2012, 2 (1), 21?31. http://dx.doi.org/10.4236/ajmb.2012.21003
42. Minchenko D. O., Danilovskyi S. V., Kryvdiuk I. V., Hlushchak N. A., Kovalevska O. V., Karbovskyi L. L., Minchenko O. H. Acute L-glutamine deprivation affects the expression of TP53-related protein genes in U87 glioma cells. Fiziol. Zh. 2014, 60 (4), 11–21.
43. Minchenko D. O., Kharkova A. P., Tsymbal D. O., Karbovskyi L. L., Minchenko O. H. Inhibition of IRE1 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?197. doi:10.4149/endo_2015_ 04_185.