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http://dx.doi.org/10.5483/BMBRep.2012.45.5.299

High sensitivity of embryonic stem cells to proteasome inhibitors correlates with low expression of heat shock protein and decrease of pluripotent cell marker expression  

Park, Jeong-A (Department of Biochemistry, College of Natural Sciences, Chungbuk National University)
Kim, Young-Eun (Department of Biochemistry, College of Natural Sciences, Chungbuk National University)
Ha, Yang-Hwa (Department of Biochemistry, College of Natural Sciences, Chungbuk National University)
Kwon, Hyung-Joo (Center for Medical Science Research, College of Medicine, Hallym University)
Lee, Young-Hee (Department of Biochemistry, College of Natural Sciences, Chungbuk National University)
Publication Information
BMB Reports / v.45, no.5, 2012 , pp. 299-304 More about this Journal
Abstract
The ubiquitin-proteasome system is a major proteolytic system for nonlysosomal degradation of cellular proteins. Here, we investigated the response of mouse embryonic stem (ES) cells under proteotoxic stress. Proteasome inhibitors induced expression of heat shock protein 70 (HSP70) in a concentration- and time-dependent manner, and also induced apoptosis of ES cells. Importantly, more apoptotic cells were observed in ES cells compared with other somatic cells. To understand this phenomenon, we further investigated the expression of HSP70 and pluripotent cell markers. HSP70 expression was more significantly increased in somatic cells than in ES cells, and expression levels of pluripotent cell markers such as Oct4 and Nanog were decreased in ES cells. These results suggest that higher sensitivity of ES cells to proteotoxic stress may be related with lower capacity of HSP70 expression and decreased pluripotent cell marker expression, which is essential for the survival of ES cells.
Keywords
Apoptosis; Embryonic stem cells; HSP70; Proteasome inhibitors; Sensitivity;
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1 Evans, M. J. and Kaufman, M. H. (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-156.   DOI   ScienceOn
2 Lumelsky, N., Blondel, O., Laeng, P., Velasco, I., Ravin, R. and McKay, R. (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292, 1389-1394.   DOI   ScienceOn
3 Xu, H., Wang, W., Li, C., Yu, H., Yang, A., Wang, B. and Jin, Y. (2009) WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells. Cell Res. 19, 561-573.   DOI   ScienceOn
4 Ramakrishna, S., Suresh, B., Lim, K. H., Cha, B. H., Lee, S. H., Kim, K. S. and Baek, K. H. (2011) PEST motif sequence regulating human NANOG for proteasomal degradation. Stem Cells Dev. 20, 1511-1519.   DOI   ScienceOn
5 Babaie, Y., Herwig, R., Greber, B., Brink, T. C., Wruck, W., Groth, D., Lehrach, H., Burdon, T. and Adjaye, J. (2007) Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells. Stem Cells 25, 500-510.   DOI   ScienceOn
6 Assou, S., Cerecedo, D., Tondeur, S., Pantesco, V., Hovatta, O., Klein, B., Hamamah, S. and De Vos, J. (2009). A gene expression signature shared by human mature oocytes and embryonic stem cells. BMC Genomics 10, 10.   DOI   ScienceOn
7 Beere, H. M., Wolf, B. B., Cain, K., Mosser, D. D., Mahboubi, A., Kuwana, T., Tailor, P., Morimoto, R. I., Cohen, G. M. and Green, D. R. (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase- 9 to the Apaf-1 apoptosome. Nat. Cell. Biol. 2, 469-475.   DOI   ScienceOn
8 Guo, Y., Mantel, C., Hromas, R. A. and Broxmeyer, H. E. (2008) Oct-4 is critical for survival/antiapoptosis of murine embryonic stem cells subjected to stress: effects associated with Stat3/survivin. Stem. Cells 26, 30-34.   DOI   ScienceOn
9 Kim,Y. E., Kang, H. B., Park, J. A., Nam, K. H., Kwon, H. J. and Lee, Y. (2008) Upregulation of NF-kappaB upon differentiation of mouse embryonic stem cells. BMB Rep. 41, 705-709.   DOI   ScienceOn
10 Gurbuxani, S., Schmitt, E., Cande, C., Parcellier, A., Hammann, A., Daugas, E., Kouranti, I., Spahr, C., Pance, A., Kroemer, G. and Garrido, C. (2003) Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor. Oncogene 22, 6669-6678.   DOI   ScienceOn
11 Naujokat, C. and Sarić, T. (2007) Concise review: role and function of the ubiquitin-proteasome system in mammalian stem and progenitor cells. Stem Cells 25, 2408-2018.   DOI   ScienceOn
12 Wojcik, C. (1999) Proteasomes in apoptosis: villains or guardians? Cell. Mol. Life Sci. 56, 908-917.   DOI
13 Boheler, K. R. (2007) Stem cell pluripotency: a cellular trait that depends on transcription factors, chromatin state and a checkpoint deficient cell cycle. J. Cell Physiol. 221, 10-17.
14 Han, M. K., Song, E. K., Guo, Y., Ou, X., Mantel, C. and Broxmeyer, H. E. (2008) SIRT1 regulates apoptosis and Nanog expression in mouse embryonic stem cells by controlling p53 subcellular localization. Cell Stem Cell 2, 241-251.   DOI   ScienceOn
15 Chen, T., Du, J. and Lu, G. (2012) Cell growth arrest and apoptosis induced by Oct4 or Nanog knockdown in mouse embryonic stem cells: a possible role of Trp53. Mol. Biol. Rep. 39, 1855-1861.   DOI
16 Meiners, S., Ludwig, A., Stangl, V. and Stangl, K. (2008) Proteasome inhibitors: poisons and remedies. Med. Res. Rev. 28, 309-327.   DOI   ScienceOn
17 Xu, H. M., Liao, B., Zhang, Q. J., Wang, B. B., Li, H., Zhong, X. M., Sheng, H. Z., Zhao, Y. X., Zhao, Y. M. and Jin, Y. (2004) Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination. J. Biol. Chem. 279, 23495-23503.   DOI   ScienceOn
18 Bjorklund, L. M., Sanchez-Pernaute, R., Chung, S., Andersson, T., Chen, I. Y., McNaught, K. S., Brownell, A. L., Jenkins, B. G., Wahlestedt, C., Kim, K. S. and Isacson, O. (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc. Natl. Acad. Sci. U.S.A. 99, 2344-2349.   DOI   ScienceOn
19 Bjorklund, A. and Lindvall, O. (2000) Cell replacement therapies for central nervous system disorders. Nat. Neurosci. 3, 537-544.   DOI   ScienceOn
20 Glickman, M. H. and Ciechanover, A. (2002) The ubiquitin- proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev. 82, 373-428.
21 Voellmy, R. and Boellmann, F. (2007) Chaperone regulation of the heat shock protein response. Adv. Exp. Med. Biol. 594, 89-99.   DOI
22 Awasthi, N. and Wagner, B. J. (2005) Upregulation of heat shock protein expression by proteasome inhibition: an antiapoptotic mechanism in the lens. Invest. Ophthalmol. Vis. Sci. 46, 2082-2091.   DOI   ScienceOn
23 Drexler, H. C., Risau, W. and Konerding, M. A. (2000) Inhibition of proteasome function induces programmed cell death in proliferating endothelial cells. FASEB J. 14, 65-77.
24 Macario, A. J. and Conway de Macario, E. (2007) Molecular chaperones multiple functions, pathologies, and potential applications. Front. Biosci. 12, 2588-2600.   DOI
25 Beckmann, R. P., Mizzen, L. E. and Welch, W. J. (1990) Interaction of Hsp 70 with newly synthesized proteins: implications for protein folding and assembly. Science 248, 850-854.   DOI   ScienceOn
26 Nollen, E. A. and Morimoto, R. I. (2002) Chaperoning signaling pathways: molecular chaperones as stress-sensing ''heat shock'' proteins. J. Cell. Sci. 115, 2809-2816.