Research Article
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Year 2022, , 92 - 98, 31.12.2022
https://doi.org/10.30782/jrvm.1131148

Abstract

References

  • 1. Blair K, Wray J, Smith A. The Liberation of Embryonic Stem Cells. PLoS Genet. 2011; 7(4).
  • 2. Weinberger L, Ayyash M, Novershtern N, Hanna JH. Dynamic stem cell states: naive to primed pluripotency in rodents and humans. Nat Rev Mol Cell Biol. 2016;17:155-169.
  • 3. Lee YM, Jeong CH, Koo SH, et al. Determination of hypoxic region by hypoxia marker in developing mouse embryos in vivo: A possible signal for vessel development. Dev Dyn. 2001;220(2):175-86.
  • 4. Manganelli G, Fico A, Masullo U, Pizzolongo F, Cimmino A, Filosa S. Modulation of the pentose phosphate pathway induces endodermal differentiation in embryonic stem cells. PLoS One. 2012;7:e29321.
  • 5. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029-1033.
  • 6. Zhou W, Choi M, Margineantu D, et al. HIF1α induced switch from bivalent to exclusively glycolytic metabolism during ESC-to-EpiSC/hESC transition. Embo J. 2012; 31(9):2103-2116.
  • 7. Dunwoodie S.L. The role of hypoxia in development of the Mammalian embryo. Dev Cell. 2009;17:755-773.
  • 8. Simon MC, Keith B. The role of oxygen availability in embryonic development and stem cell function. Nat Rev Mol Cell Biol. 2008;9:285-296.
  • 9. Ochocki JD, Simon MC. Nutrient-sensing pathways and metabolic regulation in stem cells. J Cell Biol. 2013;203(1):23-33.
  • 10. Tsogtbaatar E, Landin C, Minter-Dykhouse K, et al. Energy Metabolism Regulates Stem Cell Pluripotency. Front Cell Dev Biol. 2020;8:87.
  • 11. Kondoh, H. Cellular life span and the Warburg effect. Exp Cell Res. 2008;314:1923-1928.
  • 12. Guda MR, Asuthkar S, Labak CM, et al. Targeting PDK4 inhibits breast cancer metabolism. Am J Cancer Res. 2018;8:1725-1738.
  • 13. Wang J, Qian Y, Gao M. Overexpression of PDK4 is associated with cell proliferation, drug resistance and poor prognosis in ovarian cancer. Cancer Manag Res. 2019;11:251-262.
  • 14. Yang C, Wang S, Ruan H, et al. Downregulation of PDK4 increases lipogenesis and associates with poor prognosis in hepatocellular carcinoma. J Cancer. 2019;10:918-926.
  • 15. Tambe Y, Terado T, Kim CJ, et al. Antitumor activity of potent pyruvate dehydrogenase kinase 4 inhibitors from plants in pancreatic cancer. Mol Carcinog. 2019;58:1726-1737.
  • 16. Cui L, Cheng Z, Liu Y, et al. Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia. Cancer Gene Ther. 2020;27:15-21.
  • 17. Feng Y, Lin J, Liu Y, et al. Investigation of expressions of PDK1, PLK1 and c-Myc in diffuse large B-cell lymphoma. Int J Exp Pathol. 2019;100:32-40.
  • 18. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029-1033.
  • 19. Jeoung NH. Pyruvate dehydrogenase kinases: therapeutic targets for diabetes and cancers. Diabetes Metab J. 2015;39:188-197.
  • 20. Gudi R, Bowker-Kinley MM, Kedishvili NY, et al. Diversity of the pyruvate dehydrogenase kinase gene family in humans. J Biol Chem.1995;270(48):28989-94.
  • 21. Varum S, Rodrigues AS, Moura MB, et al. Energy Metabolism in Human Pluripotent Stem Cells and Their Differentiated Counterparts. Plos One. 2011;6(6):e20914.
  • 22. Mandal S, Lindgren AG, Srivastava AS, et al. Mitochondrial function controls proliferation and early differentiation potential of embryonic. Stem Cells. 2011;29:486-495.
  • 23. Panopoulos AD, Izpisua Belmonte JC. Anaerobicizing into pluripotency. Cell Metab. 2011;14:143-144.
  • 24. Harris RA, Bowker-Kinley MM, Huang B. Regulation of the activity of the pyruvate dehydrogenase complex. Adv Enzyme Regul. 2002;42:249-259.
  • 25. Tokmakov AA, Terazawa Y, Ikeda M, et al. Comparative expression analysis of multiple PDK genes in Xenopus laevis during oogenesis, maturation, fertilization, and early embryogenesis. Gene Expr Patterns. 2009;9(3):158-165.
  • 26. Fritsch MK, Singer DB. Embryonic stem cell biology. Adv Pediatr. 2008;55:43-77.
  • 27. Zhang S, Cui W. Sox2, a key factor in the regulation of pluripotency and neural differentiation. World J Stem Cells. 2014;6(3):305-311.
  • 28. Klimmeck D, Hansson J, Raffel S, Vakhrushev SY, Trumpp A, Krijgsveld J. Proteomic cornerstones of hematopoietic stem cell differentiation: distinct signatures of multipotent progenitors and myeloid committed cells. Mol Cell Proteomics. 2012;11:286-302.
  • 29. Halvarsson C, Eliasson P, JoÈnsson J. Pyruvate dehydrogenase kinase 1 is essential for transplantable mouse bone marrow hematopoietic stem cell and progenitor function. PLoS ONE. 2017;12(2):e0171714.
  • 30. Takubo K, Nagamatsu G, Kobayashi CI, et al. Regulation of Glycolysis by Pdk Functions as a Metabolic Checkpoint for Cell Cycle Quiescence in Hematopoietic Stem Cells. Cell Stem Cell. 2013;12(1):49-61.
  • 31. Wang H, Shan XB, Qiao YJ. PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway. Braz J Med Biol Res. 2017;50(2):e5988.
  • 32. Liu X, Zuo R, Bao Y, et al. Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts. Sci Rep. 2017;7:8474.

Changes in the Expression of Pyruvate Dehydrogenase Kinase Isoenzymes During Early Differentiation of Mouse Embryonic Stem Cells

Year 2022, , 92 - 98, 31.12.2022
https://doi.org/10.30782/jrvm.1131148

Abstract

The embryonic stem cells (ESCs) are pluripotent, self-renewing cells that able to differentiate into any of the germ layers involved in embryogenesis. However, the molecular mechanisms that control ESC pluripotency and differentiation remain poorly understood. The family of Pyruvate dehydrogenase kinase (PDK1-4), inactivates the mitochondrial pyruvate dehydrogenase complex via phosphorylation, plays a crucial role in the control of glucose homeostasis. In the current study, gene expression levels of PDK isoenzymes were analyzed on undifferentiated mouse embryonic stem cells (mESCs) and compared to mESCs induced to differentiate by removal of leukemia inhibitory factor (LIF) for 1, 3 and 5 days. Besides, we performed gene expression analysis of several genes related to pluripotency and differentiation. In addition, we also determined glucose uptake rates by a colorimetric assay kit in early differentiated and undifferentiated mESCs. Differently expression level of PDK isoenzymes in pluripotent and LIF-depleted mESCs suggest that they may have roles in differentiation and pluripotency of ESCs. Furthermore, this study lays the foundation for detailed investigation of molecular mechanisms underlying the roles of PDKs in the pluripotency and transition to differentiated state of ESCs.

References

  • 1. Blair K, Wray J, Smith A. The Liberation of Embryonic Stem Cells. PLoS Genet. 2011; 7(4).
  • 2. Weinberger L, Ayyash M, Novershtern N, Hanna JH. Dynamic stem cell states: naive to primed pluripotency in rodents and humans. Nat Rev Mol Cell Biol. 2016;17:155-169.
  • 3. Lee YM, Jeong CH, Koo SH, et al. Determination of hypoxic region by hypoxia marker in developing mouse embryos in vivo: A possible signal for vessel development. Dev Dyn. 2001;220(2):175-86.
  • 4. Manganelli G, Fico A, Masullo U, Pizzolongo F, Cimmino A, Filosa S. Modulation of the pentose phosphate pathway induces endodermal differentiation in embryonic stem cells. PLoS One. 2012;7:e29321.
  • 5. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029-1033.
  • 6. Zhou W, Choi M, Margineantu D, et al. HIF1α induced switch from bivalent to exclusively glycolytic metabolism during ESC-to-EpiSC/hESC transition. Embo J. 2012; 31(9):2103-2116.
  • 7. Dunwoodie S.L. The role of hypoxia in development of the Mammalian embryo. Dev Cell. 2009;17:755-773.
  • 8. Simon MC, Keith B. The role of oxygen availability in embryonic development and stem cell function. Nat Rev Mol Cell Biol. 2008;9:285-296.
  • 9. Ochocki JD, Simon MC. Nutrient-sensing pathways and metabolic regulation in stem cells. J Cell Biol. 2013;203(1):23-33.
  • 10. Tsogtbaatar E, Landin C, Minter-Dykhouse K, et al. Energy Metabolism Regulates Stem Cell Pluripotency. Front Cell Dev Biol. 2020;8:87.
  • 11. Kondoh, H. Cellular life span and the Warburg effect. Exp Cell Res. 2008;314:1923-1928.
  • 12. Guda MR, Asuthkar S, Labak CM, et al. Targeting PDK4 inhibits breast cancer metabolism. Am J Cancer Res. 2018;8:1725-1738.
  • 13. Wang J, Qian Y, Gao M. Overexpression of PDK4 is associated with cell proliferation, drug resistance and poor prognosis in ovarian cancer. Cancer Manag Res. 2019;11:251-262.
  • 14. Yang C, Wang S, Ruan H, et al. Downregulation of PDK4 increases lipogenesis and associates with poor prognosis in hepatocellular carcinoma. J Cancer. 2019;10:918-926.
  • 15. Tambe Y, Terado T, Kim CJ, et al. Antitumor activity of potent pyruvate dehydrogenase kinase 4 inhibitors from plants in pancreatic cancer. Mol Carcinog. 2019;58:1726-1737.
  • 16. Cui L, Cheng Z, Liu Y, et al. Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia. Cancer Gene Ther. 2020;27:15-21.
  • 17. Feng Y, Lin J, Liu Y, et al. Investigation of expressions of PDK1, PLK1 and c-Myc in diffuse large B-cell lymphoma. Int J Exp Pathol. 2019;100:32-40.
  • 18. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029-1033.
  • 19. Jeoung NH. Pyruvate dehydrogenase kinases: therapeutic targets for diabetes and cancers. Diabetes Metab J. 2015;39:188-197.
  • 20. Gudi R, Bowker-Kinley MM, Kedishvili NY, et al. Diversity of the pyruvate dehydrogenase kinase gene family in humans. J Biol Chem.1995;270(48):28989-94.
  • 21. Varum S, Rodrigues AS, Moura MB, et al. Energy Metabolism in Human Pluripotent Stem Cells and Their Differentiated Counterparts. Plos One. 2011;6(6):e20914.
  • 22. Mandal S, Lindgren AG, Srivastava AS, et al. Mitochondrial function controls proliferation and early differentiation potential of embryonic. Stem Cells. 2011;29:486-495.
  • 23. Panopoulos AD, Izpisua Belmonte JC. Anaerobicizing into pluripotency. Cell Metab. 2011;14:143-144.
  • 24. Harris RA, Bowker-Kinley MM, Huang B. Regulation of the activity of the pyruvate dehydrogenase complex. Adv Enzyme Regul. 2002;42:249-259.
  • 25. Tokmakov AA, Terazawa Y, Ikeda M, et al. Comparative expression analysis of multiple PDK genes in Xenopus laevis during oogenesis, maturation, fertilization, and early embryogenesis. Gene Expr Patterns. 2009;9(3):158-165.
  • 26. Fritsch MK, Singer DB. Embryonic stem cell biology. Adv Pediatr. 2008;55:43-77.
  • 27. Zhang S, Cui W. Sox2, a key factor in the regulation of pluripotency and neural differentiation. World J Stem Cells. 2014;6(3):305-311.
  • 28. Klimmeck D, Hansson J, Raffel S, Vakhrushev SY, Trumpp A, Krijgsveld J. Proteomic cornerstones of hematopoietic stem cell differentiation: distinct signatures of multipotent progenitors and myeloid committed cells. Mol Cell Proteomics. 2012;11:286-302.
  • 29. Halvarsson C, Eliasson P, JoÈnsson J. Pyruvate dehydrogenase kinase 1 is essential for transplantable mouse bone marrow hematopoietic stem cell and progenitor function. PLoS ONE. 2017;12(2):e0171714.
  • 30. Takubo K, Nagamatsu G, Kobayashi CI, et al. Regulation of Glycolysis by Pdk Functions as a Metabolic Checkpoint for Cell Cycle Quiescence in Hematopoietic Stem Cells. Cell Stem Cell. 2013;12(1):49-61.
  • 31. Wang H, Shan XB, Qiao YJ. PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway. Braz J Med Biol Res. 2017;50(2):e5988.
  • 32. Liu X, Zuo R, Bao Y, et al. Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts. Sci Rep. 2017;7:8474.
There are 32 citations in total.

Details

Primary Language English
Subjects Veterinary Surgery
Journal Section Research Articles
Authors

Saime Güzel 0000-0003-0796-5000

Publication Date December 31, 2022
Acceptance Date September 12, 2022
Published in Issue Year 2022

Cite

APA Güzel, S. (2022). Changes in the Expression of Pyruvate Dehydrogenase Kinase Isoenzymes During Early Differentiation of Mouse Embryonic Stem Cells. Journal of Research in Veterinary Medicine, 41(2), 92-98. https://doi.org/10.30782/jrvm.1131148
AMA Güzel S. Changes in the Expression of Pyruvate Dehydrogenase Kinase Isoenzymes During Early Differentiation of Mouse Embryonic Stem Cells. J Res Vet Med. December 2022;41(2):92-98. doi:10.30782/jrvm.1131148
Chicago Güzel, Saime. “Changes in the Expression of Pyruvate Dehydrogenase Kinase Isoenzymes During Early Differentiation of Mouse Embryonic Stem Cells”. Journal of Research in Veterinary Medicine 41, no. 2 (December 2022): 92-98. https://doi.org/10.30782/jrvm.1131148.
EndNote Güzel S (December 1, 2022) Changes in the Expression of Pyruvate Dehydrogenase Kinase Isoenzymes During Early Differentiation of Mouse Embryonic Stem Cells. Journal of Research in Veterinary Medicine 41 2 92–98.
IEEE S. Güzel, “Changes in the Expression of Pyruvate Dehydrogenase Kinase Isoenzymes During Early Differentiation of Mouse Embryonic Stem Cells”, J Res Vet Med, vol. 41, no. 2, pp. 92–98, 2022, doi: 10.30782/jrvm.1131148.
ISNAD Güzel, Saime. “Changes in the Expression of Pyruvate Dehydrogenase Kinase Isoenzymes During Early Differentiation of Mouse Embryonic Stem Cells”. Journal of Research in Veterinary Medicine 41/2 (December 2022), 92-98. https://doi.org/10.30782/jrvm.1131148.
JAMA Güzel S. Changes in the Expression of Pyruvate Dehydrogenase Kinase Isoenzymes During Early Differentiation of Mouse Embryonic Stem Cells. J Res Vet Med. 2022;41:92–98.
MLA Güzel, Saime. “Changes in the Expression of Pyruvate Dehydrogenase Kinase Isoenzymes During Early Differentiation of Mouse Embryonic Stem Cells”. Journal of Research in Veterinary Medicine, vol. 41, no. 2, 2022, pp. 92-98, doi:10.30782/jrvm.1131148.
Vancouver Güzel S. Changes in the Expression of Pyruvate Dehydrogenase Kinase Isoenzymes During Early Differentiation of Mouse Embryonic Stem Cells. J Res Vet Med. 2022;41(2):92-8.