Metabolic state alteration of neural stem cells controls FAS-mediated apoptosis and neurogenesis
Affiliation(s)
Department of Mechanical Engineering, University of Colorado at Colorado Springs, Colorado Springs, USA.
Department of Mechanical Engineering, University of Colorado at Colorado Springs, Colorado Springs, USA.
ABSTRACT
Metabolic stress causes an increased Fas-FasL (receptor-ligand pair) expression in Neural Stem Cells (NSCs) leading to Fas-induced apoptosis. In this study, we discuss the exposure of NSCs to different metabolic treatments that provoke cellular stress responses. We demonstrate that challenging cultured NSCs to ethanol (ETOH) increased cellular death via Fas-mediated apoptosis. Moreover, we establish that NSCs cultured under low lipid conditions, in which they were deprived of essential fatty acids, demonstrated increased cellular survival rates suggesting an increased ability for these lipid-starved cells to endure a stressed environment. This was further confirmed by exposing NSCs to low glucose levels and observing a decrease in percent death in low lipid NSCs. When stressed, NSCs have increased reactive oxygen levels and are susceptible to apoptosis. These findings indicate that under starved and stressed conditions, and in the presence of Fas Ligand (FasL), NSCs pursue fatty acid oxidation by burning fat as fuel. This may be the key to better understand the metabolic states of brain tumors and the characteristics of cancer.
Cite this paper
Almemar, Z. , Urban, N. and Lauderbaugh, L. (2013) Metabolic state alteration of neural stem cells controls FAS-mediated apoptosis and neurogenesis. Advances in Bioscience and Biotechnology, 4, 1-8. doi: 10.4236/abb.2013.410A1001.
Almemar, Z. , Urban, N. and Lauderbaugh, L. (2013) Metabolic state alteration of neural stem cells controls FAS-mediated apoptosis and neurogenesis. Advances in Bioscience and Biotechnology, 4, 1-8. doi: 10.4236/abb.2013.410A1001.
References
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http://dx.doi.org/10.1038/jcbfm.2008.61 [15] Geuna, S., Borriione, P., Fornaro, M. and Giacobini-Robecchi, M.G. (2001) Adult stem cells and neurogenesis: Historical roots and state of the art. The Anatomical Record, 265, 132-141. http://dx.doi.org/10.1002/ar.1135 [16] Cao, Q., Benton, R.L. and Wittemore, S.R. (2002) Stem cell repair of central nervous system injury. Journal of Neuroscience Research, 68, 501-510.
http://dx.doi.org/10.1002/jnr.10240 [17] Horie, N., Moriya, T., Mitome, M., Kitagawa, N., Nagata, I. and Shinohara, K. (2004) Lowered glucose suppressed the proliferation and increased the differentiation of murine neural stem cells in vitro. FEBS Letters, 571, 37-242.
http://dx.doi.org/10.1016/j.febslet.2004.06.085 [18] Wu, Z., Huang, K., Yu, J. H., Le, T., Namihira, M., Liu, Y., Zhang, J., Xue, Z., Cheng, L. and Fan, G. (2012) Dnmt3a regulates both proliferation and differentiation of mouse neural stem cells. Journal of Neuroscience Research, 90, 1883-1891. [19] Newell, M.K., Melamede, R., Villalobos-Menuey, E., Swartzendruber, D., Trauger, R., Camley, R.E. and Crisp, W. (2004) The effects of chemotherapeutics on cellular metabolism and consequent immune recognition. Journal of Immune Based Therapies and Vaccines, 2, 1-6.
http://dx.doi.org/10.1186/1476-8518-2-3 [20] Zimmermann, K.C., Bonzon, C. and Green, D.R. (2001) The machinery of programmed cell death. Pharmacology and Therapeutics, 92, 57-70.
http://dx.doi.org/10.1016/S0163-7258(01)00159-0 [21] Strasser, A., Jost, P.J. and Nagata, S. (2009) The many roles of FAS receptor signaling in the immune system. Immunity, 30, 180-192.
http://dx.doi.org/10.1016/j.immuni.2009.01.001 [22] Mahmood, Z. and Shukla, Y. (2010) Death receptors: Targets for cancer therapy. Experimental Cell Research, 6, 887-899. http://dx.doi.org/10.1016/j.yexcr.2009.12.011 [23] Corsini, N.S., Sancho-Martinez, I., Laudenklos, S., Glagow, D., Kumar, S., Letellier, E., Koch, P., Teodorczyk, M., Kleber, S., Klussmann, S., Wiestler B., Brustle O., Mueller, W., Gieffers, C., Hill, O., Thiemann, M., Seedorf, M., Gretz, N., Sprengel, R., Celikel, T. and Martin-Villalba, A. (2009) The death receptor CD95 activates adult neural stem cells for working memory formation and brain repair. Cell Stem Cell, 5, 178-190.
http://dx.doi.org/10.1016/j.stem.2009.05.004 [24] Knight, J.C., Scharf, E.L. and Draayer, Y. (2010) Fas activation increases neural progenitor cell survival. Journal of Neuroscience Research, 88, 746-757. [25] Schweitzer, S.C., Reding, A.M., Patton, H.M., Sullivan, T.P., Stubbs, C.E., Villalobos-Manuey, E., Huber, S.A. and Newell, M.K. (2006) Endogenous versus exogenous fatty acid availability affects lysosomal acidity and MHC class II expression. Journal of Lipid Research, 47, 2525-2537.
http://dx.doi.org/10.1194/jlr.M600329-JLR200 [26] Nixon, R., Mathews, P.M. and Cataldo, A.M. (2001) The neuronal endosomal-lysosomal system in alzheimer’s disease. Journal of Alzheimer’s Disease, 3, 97-107. [27] Shapiro, H.M. (2003) Practical flow cytometry. John Wiley & Sons Inc., Hoboken, 225-256. [28] Pajusto, M., Tarkkanen, J. and Mattila, P.S. (2005) Human primary adenotonsillar naive phenotype CD45RA+ CD4+ T lymphocytes undergo apoptosis upon stimulation with a high concentration of CD3 antibody. Scaninavian Journal of Immunology, 62, 546-551.
http://dx.doi.org/10.1111/j.1365-3083.2005.01697.x [29] Ryder, E.F., Snyder, E.Y. and Cepko, C.L. (1990) Establishment and characterization of mulipotent neural cell lines using retrovirus vector-mediated oncogene transfer. Journal of Neurobiology, 21, 356-375.
http://dx.doi.org/10.1002/neu.480210209
[1] Reynolds, B.A. and Weiss, S. (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 255, 1707-1710.
http://dx.doi.org/10.1126/science.1553558 [2] Gage, F.H., Coates, P.W., Palmer, T.D., Kuhn, H.G., Fisher, L.J., Suhonen, J.O., Peterson, D.A., Suhr, S.T. and Ray, J. (1995) Survival and differentiation of adult neuronal progenitor cells tranplanted to the adult brain. Proceedings of the National Academy of Sciences, 92, 11879-11883. http://dx.doi.org/10.1073/pnas.92.25.11879 [3] Taupin, P. and Gage, F.H. (2002) Adult neurogenesis and neural stem cells of the central nervous system in mammals. Journal of Neuroscience Research, 69, 745-749.
http://dx.doi.org/10.1002/jnr.10378 [4] Harper, M., Antoniou, A., Villalobos-Menuey, E., Russo, A., Trauger, R., Vendemelio, M., George, A., Bartholomew, R., Carlo, D., Shaikh, A., Kupperman, J., Newell, E., Bespalov, I., Wallace, S., Liu, Y., Rogers, J., Gibbs, G., Leahy, J., Camley, R., Melamede, R. and Newell, K. (2002) Characterization of a novel metabolic strategy used by drug-resistant tumor cells. The FASEB Journal, 16, 1550-1557. http://dx.doi.org/10.1096/fj.02-0541com [5] Vangipuram, S.D. and Lyman, W.D. (2010) Ethanol alters cell fate of fetal human brain-derived stem and progenitor cells. Alcoholism: Clinical and Experimental Research, 34, 1574-1583.
http://dx.doi.org/10.1111/j.1530-0277.2010.01242.x [6] Kim, K.C., Go, H.S., Bak, H.R., Choi, C.S., Choi, I., Kim, P., Han, S., Han, S.M., Shin, C.Y. and Ko, K.H. (2010) Prenatal exposure of ethanol induces increased glutamatergic neuronal differentiation of neural progenitor cells. Journal of Biomedical Science, 17, 1-9.
http://dx.doi.org/10.1186/1423-0127-17-85 [7] Prock, T.L. and Miranda, R.C. (2007) Embryonic cerebral cortical progenitors are resistant to apoptosis, but increase expression of suicide receptor DISC-complex genes and suppress autophagy following ethanol exposure. Alcoholism: Clinical and Experimental Research, 31, 694-703. [8] Dikranian, K., Quin, Y., Labruyere, J., Nemmers, B. and Olney, J.W. (2005) Ethanol-induced neuroapoptosis in the developing rodent cerebellum and related brain stem structures. Developmental Brain Research, 155, 1-13.
http://dx.doi.org/10.1016/j.devbrainres.2004.11.005 [9] Ceccatelli, S., Tamm, C., Sleeper, E. and Orrenius, S. (2004) Neural stem cells and cell death. Toxicology Letter, 149, 59-66. http://dx.doi.org/10.1016/j.toxlet.2003.12.060 [10] Moreno-Sanchez, R., Saavedra, E., Rodriguez-Enriquez, S., Gallardo-Perez, J.C., Quezada, H. and Westerhoff, H.V. (2010) Metabolic control analysis indicates a change of strategy in the treatment of cancer. Mitochondrion, 10, 626-639. http://dx.doi.org/10.1016/j.mito.2010.06.002 [11] Cavaliere, F., D’Ambrosi, N., Sancesario, G., Bernardi, G. and Volonte, C. (2001) Hypoglycaemia-induced cell death: Features of neuroprotection by the P2 receptor antagonist basilen blue. Neurochemistry International, 38, 199-207.
http://dx.doi.org/10.1016/S0197-0186(00)00087-5 [12] Auer, R.N. (1986) Progress review: Hypoglycemic brain damage. Stroke, 17, 699-708.
http://dx.doi.org/10.1161/01.STR.17.4.699 [13] Mitchell, J.J., Paiva, M., Moore, D.B., Walker, D.W. and Heaton, M.B. (1998) A comparative study of ethanol, hypoglycemia, hypoxia and neurotrophic factor interactions with fetal rat hippocampal neurons: A multi-factor in vitro model for developmental ethanol effects. Developmental Brain Research, 105, 241-250.
http://dx.doi.org/10.1016/S0165-3806(97)00182-X [14] Suh, S.W., Hamby, A.M., Gum, E.T., Shin, B.S., Won, S.J., Sheline, C.T., Chan, P.H. and Swanson, R.A. (2008) Sequential release of nitric oxide, zinc and superoxide in hypoglycemic neuronal death. Journal of Cerebral Blood Flow and Metabolism, 28, 1697-1706.
http://dx.doi.org/10.1038/jcbfm.2008.61 [15] Geuna, S., Borriione, P., Fornaro, M. and Giacobini-Robecchi, M.G. (2001) Adult stem cells and neurogenesis: Historical roots and state of the art. The Anatomical Record, 265, 132-141. http://dx.doi.org/10.1002/ar.1135 [16] Cao, Q., Benton, R.L. and Wittemore, S.R. (2002) Stem cell repair of central nervous system injury. Journal of Neuroscience Research, 68, 501-510.
http://dx.doi.org/10.1002/jnr.10240 [17] Horie, N., Moriya, T., Mitome, M., Kitagawa, N., Nagata, I. and Shinohara, K. (2004) Lowered glucose suppressed the proliferation and increased the differentiation of murine neural stem cells in vitro. FEBS Letters, 571, 37-242.
http://dx.doi.org/10.1016/j.febslet.2004.06.085 [18] Wu, Z., Huang, K., Yu, J. H., Le, T., Namihira, M., Liu, Y., Zhang, J., Xue, Z., Cheng, L. and Fan, G. (2012) Dnmt3a regulates both proliferation and differentiation of mouse neural stem cells. Journal of Neuroscience Research, 90, 1883-1891. [19] Newell, M.K., Melamede, R., Villalobos-Menuey, E., Swartzendruber, D., Trauger, R., Camley, R.E. and Crisp, W. (2004) The effects of chemotherapeutics on cellular metabolism and consequent immune recognition. Journal of Immune Based Therapies and Vaccines, 2, 1-6.
http://dx.doi.org/10.1186/1476-8518-2-3 [20] Zimmermann, K.C., Bonzon, C. and Green, D.R. (2001) The machinery of programmed cell death. Pharmacology and Therapeutics, 92, 57-70.
http://dx.doi.org/10.1016/S0163-7258(01)00159-0 [21] Strasser, A., Jost, P.J. and Nagata, S. (2009) The many roles of FAS receptor signaling in the immune system. Immunity, 30, 180-192.
http://dx.doi.org/10.1016/j.immuni.2009.01.001 [22] Mahmood, Z. and Shukla, Y. (2010) Death receptors: Targets for cancer therapy. Experimental Cell Research, 6, 887-899. http://dx.doi.org/10.1016/j.yexcr.2009.12.011 [23] Corsini, N.S., Sancho-Martinez, I., Laudenklos, S., Glagow, D., Kumar, S., Letellier, E., Koch, P., Teodorczyk, M., Kleber, S., Klussmann, S., Wiestler B., Brustle O., Mueller, W., Gieffers, C., Hill, O., Thiemann, M., Seedorf, M., Gretz, N., Sprengel, R., Celikel, T. and Martin-Villalba, A. (2009) The death receptor CD95 activates adult neural stem cells for working memory formation and brain repair. Cell Stem Cell, 5, 178-190.
http://dx.doi.org/10.1016/j.stem.2009.05.004 [24] Knight, J.C., Scharf, E.L. and Draayer, Y. (2010) Fas activation increases neural progenitor cell survival. Journal of Neuroscience Research, 88, 746-757. [25] Schweitzer, S.C., Reding, A.M., Patton, H.M., Sullivan, T.P., Stubbs, C.E., Villalobos-Manuey, E., Huber, S.A. and Newell, M.K. (2006) Endogenous versus exogenous fatty acid availability affects lysosomal acidity and MHC class II expression. Journal of Lipid Research, 47, 2525-2537.
http://dx.doi.org/10.1194/jlr.M600329-JLR200 [26] Nixon, R., Mathews, P.M. and Cataldo, A.M. (2001) The neuronal endosomal-lysosomal system in alzheimer’s disease. Journal of Alzheimer’s Disease, 3, 97-107. [27] Shapiro, H.M. (2003) Practical flow cytometry. John Wiley & Sons Inc., Hoboken, 225-256. [28] Pajusto, M., Tarkkanen, J. and Mattila, P.S. (2005) Human primary adenotonsillar naive phenotype CD45RA+ CD4+ T lymphocytes undergo apoptosis upon stimulation with a high concentration of CD3 antibody. Scaninavian Journal of Immunology, 62, 546-551.
http://dx.doi.org/10.1111/j.1365-3083.2005.01697.x [29] Ryder, E.F., Snyder, E.Y. and Cepko, C.L. (1990) Establishment and characterization of mulipotent neural cell lines using retrovirus vector-mediated oncogene transfer. Journal of Neurobiology, 21, 356-375.
http://dx.doi.org/10.1002/neu.480210209