Neurochemical Research

, Volume 43, Issue 9, pp 1841–1854 | Cite as

Exposure of Rat Neural Stem Cells to Ethanol Affects Cell Numbers and Alters Expression of 28 Proteins

  • Mohammed A. Kashem
  • Nilufa Sultana
  • Vladimir J. BalcarEmail author
Original Paper


Developing brain cells express many proteins but little is known of how their protein composition responds to chronic exposure to alcohol and/or how such changes might relate to alcohol toxicity. We used cultures derived from embryonic rat brain (previously shown to contain mostly neural stem cells; rat NSC, rNSC), exposed them to ethanol (25–100 mM) for up to 96 h and studied how they reacted. Ethanol (50 and 100 mM) reduced cell numbers indicating either compromised cell proliferation, cytotoxicity or both. Increased lipid peroxidation was consistent with the presence of oxidative stress accompanying alcohol-induced cytotoxicity. Proteomics revealed 28 proteins as altered by ethanol (50 mM for 96 h). Some were constituents of cytoskeleton, others were involved in transcription/translation, signal transduction and oxidative stress. Nucleophosmin (NPM1) and dead-end protein homolog 1 (DND1) were further studied by immunological techniques in cultured neurons and astrocytes (derived from brain tissue at embryonic ages E15 and E20, respectively). In the case of DND1 (but not NPM1) ethanol induced similar pattern of changes in both types of cells. Given the critical role of the protein NPM1 in cell proliferation and differentiation, its reduced expression in the ethanol-exposed rNSC could, in part, explain the lower cells numbers. We conclude that chronic ethanol profoundly alters protein composition of rNSC to the extent that their functioning—including proliferation and survival—would be seriously compromised. Translated to humans, such changes could point the way towards mechanisms underlying the fetal alcohol spectrum disorder and/or alcoholism later in life.


Alcohol Proteomics Stem cells NPM1 DND1 FASD 


  1. 1.
    Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL (1999) Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 2(10):861–863PubMedCrossRefGoogle Scholar
  2. 2.
    Andersen SL, Thompson AT, Rutstein M, Hostetter JC, Teicher MH (2000) Dopamine receptor pruning in prefrontal cortex during the periadolescent period in rats. Synapse 37(2):167–169PubMedCrossRefGoogle Scholar
  3. 3.
    Andersen SL, Teicher MH (2004) Delayed effects of early stress on hippocampal development. Neuropsychopharmacology 29(11):1988–1993PubMedCrossRefGoogle Scholar
  4. 4.
    Dennis CV, Suh LS, Rodriguez ML, Krill JJ, Sutherland GT (2016) Human adult neurogenesis across the ages: an immunohistochemical study. Neuropathology Appl Neurobiol 42(7):621–638. CrossRefGoogle Scholar
  5. 5.
    Cowen DS, Takase LF, Fornal CA, Jacobs BL (2008) Age-dependent decline in hippocampal neurogenesis is not altered by chronic treatment with fluoxetine. Brain Res 1228(4):14–19 doi:. PubMedCrossRefGoogle Scholar
  6. 6.
    McKay R (1997) Stem cells in the central nervous system. Science 276(5309):66–67PubMedCrossRefGoogle Scholar
  7. 7.
    Geil CR, Hayes DM, McClain JA, Liput DJ, Marshall SA, Chen KY, Nixon K (2014) Alcohol and adult hippocampal neurogenesis: Promiscuous drug, wanton effects. Prog Neuro Psychopharmacol Biol Psychiatry 54:103–113. CrossRefGoogle Scholar
  8. 8.
    Nixon K, Crews FT (2002) Binge ethanol exposure decreases neurogenesis in adult rat hippocampus. J Neurochem 83(5):1087–1093PubMedCrossRefGoogle Scholar
  9. 9.
    Herrera DG, Yague AG, Johnsen-Soriano S, Bosch-Morell F, Collado-Morente L, Muriach M, Romero FJ, Garcia-Verdugo JM (2003) Selective impairment of hippocampal neurogenesis by chronic alcoholism: protective effects of an antioxidant. Proc Nat Acad Sci USA 100(13):7919–7924PubMedCrossRefGoogle Scholar
  10. 10.
    Kvigne VL, Randall B, Simanton EG, Brenneman G, Welty TK (2012) Blood alcohol levels for American Indian mothers and newborns. Pediatrics 130(4):e1015–e1018. PubMedCrossRefGoogle Scholar
  11. 11.
    Louis LK, Gopurappilly R, Surendran H, Dutta S, Pal R (2017) Transcriptional profiling of human neural precursors post alcohol exposure reveals impair neurogenesis via dysregulation of ERK signaling and miR-145. J Neurochem. PubMedCrossRefGoogle Scholar
  12. 12.
    Crews FT, Mdzinarishvili A, Kim D, He J, Nixon K (2006) Neurogenesis in adolescent brain is potently inhibited by ethanol. Neuroscience 137(2):437–445 PubMedCrossRefGoogle Scholar
  13. 13.
    Redila VA, Olson AK, Swann SE, Mohades G, Webber AJ, Weinberg J, Christie BR (2006) Hippocampal cell proliferation is reduced following prenatal ethanol exposure but can be rescued with voluntary exercise. Hippocampus 16(3):305–311. PubMedCrossRefGoogle Scholar
  14. 14.
    Klintsova AY, Helfer JL, Calizo LH, Dong WK, Goodlett CR, Greenough WT (2007) Persistent impairment of hippocampal neurogenesis in young adult rats following early postnatal alcohol exposure. Alcoholism Clin Exp Res 31(12):2073–2082CrossRefGoogle Scholar
  15. 15.
    Tateno M, Ukai W, Hashimoto E, Ikeda H, Saito T (2006) Implication of increased NRSF/REST binding activity in the mechanisms of ethanol inhibition of neuronal differentiation. J Neural Transm 113:283–293PubMedCrossRefGoogle Scholar
  16. 16.
    Campbell JC, Stipcevic T, Flores RE, Perry C, Kippin TE (2014) Alcohol exposure inhibits adult neural stem cell proliferation. Exp Brain Res 232(9):2775–2784PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Morris SA, Eaves DW, Smith AR, Nixon K (2010) Alcohol inhibition of neurogenesis: a mechanism of hippocampal neurodegeneration in an adolescent alcohol abuse model. Hippocampus 20(5):596–607PubMedPubMedCentralGoogle Scholar
  18. 18.
    Vemuri MC, Chetty CS (2005) Alcohol impairs astrogliogenesis by stem cells in rodent neurospheres. Neurochem Internat 47(1–2):129–135CrossRefGoogle Scholar
  19. 19.
    MacDonald JL, Roskams AJ (2009) Epigenetic regulation of nervous system development by DNA methylation and histone deacetylation. Prog Neurobiol 88(3):170–183PubMedCrossRefGoogle Scholar
  20. 20.
    Witt ED (2010) Research on alcohol and adolescent brain development: opportunities and future directions. Alcohol 44(1):119–124PubMedCrossRefGoogle Scholar
  21. 21.
    Liyanage VR, Jarmasz JS, Murugeshan N, Del Bigio MR, Rastegar M, Davie JR (2014) DNA modifications: function and applications in normal and disease states. Biology 3(4):670–723PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Stragier E, Martin V, Davenas E, Poilbout C, Mongeau R, Corradetti R, Lanfumey L (2015) Brain plasticity and cognitive functions after ethanol consumption in C57BL/6J mice. Translat Psychiatry 5::e696. CrossRefGoogle Scholar
  23. 23.
    Bonnaud EM, Suberbielle E, Malnou CE (2016) Histone acetylation in neuronal (dys)function. Biomol Concepts 7(2):103–116. PubMedCrossRefGoogle Scholar
  24. 24.
    Kashem MA, James G, Harper C, Wilce P, Matsumoto I (2007) Differential protein expression in the corpus callosum (splenium) of human alcoholics: a proteomics study. Neurochem Internat 50(2):450–459CrossRefGoogle Scholar
  25. 25.
    Matsuda-Matsumoto H, Iwazaki T, Kashem MA, Harper C, Matsumoto I (2007) Differential protein expression profiles in the hippocampus of human alcoholics. Neurochem Int 51(6–7):370–376PubMedCrossRefGoogle Scholar
  26. 26.
    Matsumoto I, Alexander-Kaufman K, Iwazaki T, Kashem MA, Matsuda-Matsumoto H (2007) CNS proteomes in alcohol and drug abuse and dependence. Expert Rev Proteomics 4(4):539–552PubMedCrossRefGoogle Scholar
  27. 27.
    Kashem MA, Harper C, Matsumoto I (2008) Differential protein expression in the corpus callosum (genu) of human alcoholics. Neurochem Internat 53(1–2):1–11. CrossRefGoogle Scholar
  28. 28.
    Hargreaves GA, Quinn H, Kashem MA, Matsumoto I, McGregor IS (2009) Proteomic analysis demonstrates adolescent vulnerability to lasting hippocampal changes following chronic alcohol consumption. Alcoholism Clin Exp Res 33(1):86–94. CrossRefGoogle Scholar
  29. 29.
    Kashem MA, Etages HD, Kopitar-Jerala N, McGregor IS, Matsumoto I (2009) Differential protein expression in the corpus callosum (body) of human alcoholic brain. J Neurochem 110(2):486–495. 06141.xPubMedCrossRefGoogle Scholar
  30. 30.
    Kashem MA, Ahmed S, Sarker R, Ahmed EU, Hargreaves GA, McGregor IS (2012) Long-term daily access to alcohol alters dopamine-related synthesis and signaling proteins in the rat striatum. Neurochem Internat 61(8):1280–1288. CrossRefGoogle Scholar
  31. 31.
    Kashem MA, Ahmed S, Sultana N, Ahmed EU, Pickford R, Rae C, Sery O, McGregor IS, Balcar VJ (2016) Metabolomics of neurotransmitters and related metabolites in post-mortem tissue from the dorsal and ventral striatum of alcoholic human hrain. Neurochem Res 41(1–2):385–397. PubMedCrossRefGoogle Scholar
  32. 32.
    van Hoof D, Krijgsveld J, Mummery C (2012) Proteomic analysis of stem cell differentiation and early development. Cold Spring Harbor Persp Biol 4:a008177. CrossRefGoogle Scholar
  33. 33.
    Kashem MA, Ummehany R, Ukai W, Hashimoto E, Saito T, McGregor IS, Matsumoto I (2009) Effects of typical (haloperidol) and atypical (risperidone) antipsychotic agents on protein expression in rat neural stem cells. Neurochem Internat 55(7):558–565. CrossRefGoogle Scholar
  34. 34.
    Hansson E (1984) Cellular composition of a cerebral hemisphere primary culture. Neurochem Res 9(2):153–171PubMedCrossRefGoogle Scholar
  35. 35.
    Dichter MA (1978) Rat cortical neurons in cell culture: culture methods, cell morphology, electrophysiology and synapse formation. Brain Res 149(2):279–293PubMedCrossRefGoogle Scholar
  36. 36.
    Rodriguez FD, Simonsson P, Alling C (1992) A method for maintaining constant ethanol concentrations in cell media. Alcohol Alcoholism 27(3):309–313PubMedGoogle Scholar
  37. 37.
    Eysseric H, Gonthier B, Soubeyran A, Bessard G, Saxod R, Barret L (1997) There is no simple method to maintain a constant ethanol concentration in long-term cell culture, keys to a solution applied to the survey of astrocytic ethanol absorption. Alcohol 14(2):111–115PubMedCrossRefGoogle Scholar
  38. 38.
    Kashem MA, Sarker R, Des Etages H, Machaalani R, King N, McGregor IS, Matsumoto I (2009) Comparative proteomics in the corpus callosal sub-regions of postmortem human brain. Neurochem Internat 55(7):483–490. CrossRefGoogle Scholar
  39. 39.
    Ahmed EU, Ahmed S, Ukai W, Matsumoto I, Kemp A, McGregor IS, Kashem MA (2012) Antipsychotic induced alteration of growth and proteome of rat neural stem cells. Neurochem Res 37(8):1649–1659. PubMedCrossRefGoogle Scholar
  40. 40.
    Shin JW, Nguyen KTD, Pow DV, Knight T, Buljan V, Bennett MR, Balcar VJ (2009) Distribution of glutamate transporter GLAST in membranes of clutired astrocytes in the presence of glutamate transport substrates and ATP. Neurochem Res 34(10):1758–1766. PubMedCrossRefGoogle Scholar
  41. 41.
    Nguyen KTD, Buljan V, Else PL, Pow DV, Balcar VJ (2010) Cardiac glycosides and digoxine interfere with the regulation of glutamate trabsporter GLAST in astrocytes cultured from neonatal rat brain. Neurochem Res 35(12):2062–2069. PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Garcia YJ, Rodríguez-Malaver AJ, Peñaloza N (2005) Lipid preoxidation measurement by thiobarbituric acid assay in rat cerebellar slices. J Neurosci Methods 144(1):127–135PubMedCrossRefGoogle Scholar
  43. 43.
    Tang S, Machaalani R, Kashem MA, Matsumoto I, Waters KA (2009) Intermittent hypercapnic hypoxia induced protein changes in the piglet hippocampus identified by MALDI-TOF-MS. Neurochem Res 34(12):2215–2225. PubMedCrossRefGoogle Scholar
  44. 44.
    van Nieuwenhuijzen PS, Kashem MA, Matsumoto I, Hunt GE, McGregor IS (2010) A long hangover from party drugs: residual proteomic changes in the hippocampus of rats 8 weeks after gamma-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination. Neurochem Intern 56(8):871–877. CrossRefGoogle Scholar
  45. 45.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analyt Biochem 72:248–254PubMedCrossRefGoogle Scholar
  46. 46.
    Storey JD, Tibshirani R (2003) Statistical significance for genome wide studies. Proc Nat Acad Sci USA 100(16):9440–9445PubMedCrossRefGoogle Scholar
  47. 47.
    Lovinger DM, White G, Weight FF (1990) Ethanol inhibition of neuronal glutamate inhibition of neuronal of glutamate receptor function. Ann Med 22(4):247–252PubMedCrossRefGoogle Scholar
  48. 48.
    Spanagel R (2009) Alcoholism: a system approach from molecular physiology to addicitive behavior. Physiol Rev 89(2):649–705PubMedCrossRefGoogle Scholar
  49. 49.
    Rae CD, Davidson JE, Maher AD, Rowlands BD, Kashem MA, Nasrallah FA, Rallapalli SK, Cook JM, Balcar VJ (2014) Ethanol, not detectably metanolized in brain, significantly reduces brain metabolism, probably via action at specific GABA(A) receptors and has measurable metabolic effects at very low concentrations. J Neurochem 129(2):304–314. PubMedCrossRefGoogle Scholar
  50. 50.
    Rae CD, Balcar VJ (2014) A metabolomic multivariate statistical approach for obtaining data-driven information in neuropharmcological research. Recept Clin Investig 1(3):153–156. CrossRefGoogle Scholar
  51. 51.
    Davidson M, Shanley B, Wilce P (1995) Increased NMDA-induced excitability during ethanol withdrawal: a behavioural study. Brain Res 674(1):91–96PubMedCrossRefGoogle Scholar
  52. 52.
    Hoffman PL (1995) Glutamate receptors in alcohol withdrawal-induced neurotoxicity. Metab Brain Dis 10:73–79PubMedCrossRefGoogle Scholar
  53. 53.
    Berg DA, Belnoue L, Song H, Simon S (2013) Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain. Development 140(1):2548–2561PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Ming GL, Song H (2011) Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70(4):687–702. PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Šťastný F, Lisý V, Mareš V, Lisá V, Balcar VJ, Santamaria A (2004) Quinolinic acid induces NMDA receptor-mediated lipid peroxidation in rat brain microvessels. Redox Rep 9(4):229–233CrossRefGoogle Scholar
  56. 56.
    Garcia E, Limon D, Perez-De La Cruz V, Giordano M, Diaz-Munñz M, Maldonado PD, Herrera-Mundo MN, Pedraza-Chaverri J, Santamaría A (2008) Free Radical Res 42(10):892–902. CrossRefGoogle Scholar
  57. 57.
    Rangel-López E, Colín-Gonzales AL, Paz-Loyola AL, Pinzón E, Torres I, Serratos IN, Castellanos P, Wajner M, Souza DO, Santamaría A (2015) Cannabinoid receptor agonists reduce the short-term mitochondrial dysfunction and oxidative stress linked to excitotoxicity in the rat brain. Neuroscience 285:97–106PubMedCrossRefGoogle Scholar
  58. 58.
    Enomoto H, Nakamura H, Liu W, Nishiguchi S (2015) Hepatoma-derived gowth factor: Its possible involvement in the progression of hepatocellular carcinoma. Int J Mol Sci 16(6):14086–14097. PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Enomoto H, Nakamura H, Liu W, Iwata Y, Nishikawa H, Takata R, Yoh K, Hasegawa K, Ishii A, Takashima T, Sakai Y, Aizawa N, Ikeda N, Iijima H, Nishiguchi S (2015) Down-regulation of HDGF Inhibits the Growth of Hepatocellular Carcinoma Cells In Vitro and In Vivo. Anticancer Res 35(12):6475–6479PubMedGoogle Scholar
  60. 60.
    Zhang A, Long W, Guo Z, Cao BB (2012) Downregulation of hepatoma-derived growth factor suppresses the malignant phenotype of U87 human glioma cells. Onc Reports 28(1):62–68Google Scholar
  61. 61.
    Hsu SS, Chen CH, Liu GS, Tai MH, Wang JS, Wu JC, Kung ML, Chan EC, Liu LF (2012) Tumorigenesis and prognostic role of hepatoma-derived growth factor in human gliomas. J Neuro Oncol 107(1):101–109. CrossRefGoogle Scholar
  62. 62.
    Alexander-Kaufman K, James G, Sheedy D, Harper C, Matsumoto I (2006) Differential protein expression in the prefrontal white matter of human alcoholics: a proteomics study. Mol Psychiatry 11(1):56–65. PubMedCrossRefGoogle Scholar
  63. 63.
    Nakata K, Ujike H, Sakai A, Takaki M, Imamura T, Tanaka Y, Kuroda S (2003) The human dihydropyrimidinase-related protein 2 gene on chromosome 8p21 is associated with paranoid-type schizophrenia. Biol Psychiatry 53(7):571–576PubMedCrossRefGoogle Scholar
  64. 64.
    Johnston-Wilson NL, Sims CD, Hofmann JP, Anderson L, Shore AD, Torrey EF, Yolken RH (2000) Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. Stanley Neuropathol Consort Mol Psychiatry 5(2):142–149Google Scholar
  65. 65.
    Luo J (2014) Autophagy and ethanol neurotoxicity. Autophagy 10(12):2099–2108. PubMedCrossRefGoogle Scholar
  66. 66.
    Kato J, Zhu J, Liu C, Stylianou M, Hoffmann V, Lizak MJ, Glasgow CG, Moss J (2011) ADP-ribosylarginine hydrolase regulates cell proliferation and tumorigenesis. Cancer Res 71(15):5327–5335. PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Grisendi S, Pandolfi PP (2005) NPM mutations in acute myelogenous leukemia. New Engl J Med 352(3):291–292PubMedCrossRefGoogle Scholar
  68. 68.
    Qing Y, Yingmao G, Lujun B, Shaoling L (2008) Role of Npm1 in proliferation, apoptosis and differentiation of neural stem cells. J Neurol Sci 266(1–2):131–137PubMedCrossRefGoogle Scholar
  69. 69.
    Pfister JA, D’Mello SR (2015) Insights into the regulation of neuronal viability by nucleophosmin/B23. Exp Biol Med (Maywood) 240(6):774–786. CrossRefGoogle Scholar
  70. 70.
    Okuda M, Horn HF, Tarapore P, Tokuyama Y, Smulian AG, Chan PK, Knudsen ES, Hofmann IA, Snyder JD, Bove KE, Fukasawa K (2000) Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication. Cell 103(1):127–140PubMedCrossRefGoogle Scholar
  71. 71.
    Lindstrom MS (2011) NPM1/B23: a multifunctional chaperone in ribosome biogenesis and chromatin remodeling. Biochem Res Int 2011:195209. PubMedCrossRefGoogle Scholar
  72. 72.
    Box JK, Paquet N, Adams MN, Boucher D, Bolderson E, O’Byrne KJ, Richard DJ (2016) Nucleophosmin: from structure and function to disease development. BMC Mol Biol 17(1):19. PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Peter N, Chiramel KJ, A RS (2013) Effect of alcohol withdrawl on glutathione S-transferase, total antioxidant capacity and amylase in blood and saliva of alcohol-dependent males. J Clin Diag Res 7(5):797–800. CrossRefGoogle Scholar
  74. 74.
    Takei N, Kondo J, Nagaike K, Ohsawa K, Kato K, Kohsaka S (1991) Neuronal survival factor from bovine brain is identical to neuron-specific enolase. J Neurochem 57(4):1178–1184PubMedCrossRefGoogle Scholar
  75. 75.
    Diaz-Ramos A, Roig-Borrellas A, Garcia-Melero A, Lopez-Alemany R (2012) Alpha-Enolase, a multifunctional protein: its role in pathophysiological situations. J Biomed Biotech 2012:156795. CrossRefGoogle Scholar
  76. 76.
    Subramanian A, Miller DM (2000) Structural analysis of alpha-enolase. Mapping the functional domains involved in down-regulation of the c-myc protooncogene. J Biol Chem 275(8):5958–5965PubMedCrossRefGoogle Scholar
  77. 77.
    Fatemi SH, Earle JA, Stary JM, Lee S, Sedgewick J (2001) Altered levels of the synaptosomal associated protein SNAP-25 in hippocampus of subjects with mood disorders and schizophrenia. Neuroreport 12(15):3257–3262PubMedCrossRefGoogle Scholar
  78. 78.
    Hohenstein AC, Roche PA (2001) SNAP-29 is a promiscuous syntaxin-binding SNARE. Biochem Biophys Res Comm 285(2):167–171PubMedCrossRefGoogle Scholar
  79. 79.
    Varodayan FP, Pignataro L, Harrison NL (2011) Alcohol induces synaptotagmin 1 expression in neurons via activation of heat shock factor 1. Neuroscience 193:63–71. doi:_10.1016/j.neuroscience.2011.07.035PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Mandrekar P, Catalano D, Jeliazkova V, Kodys K (2008) Alcohol exposure regulates heat shock transcription factor binding and heat shock proteins 70 and 90 in monocytes and macrophages: implication for TNF-alpha regulation. J Leukocyte Biol 84(5):1335–1345. doi:_10.1189/jlb.0407256PubMedCrossRefGoogle Scholar
  81. 81.
    Gorini G, Roberts AJ, Mayfield RD (2013) Neurobiological signatures of alcohol dependence revealed by protein profiling. PLoS ONE 8(12):e82656. PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Nanji AA, Griniuviene B, Yacoub LK, Sadrzadeh SM, Levitsky S, McCully JD (1995) Heat-shock gene expression in alcoholic liver disease in the rat is related to the severity of liver injury and lipid peroxidation. Proc Soc Exp Biol Med 210(1):12–19PubMedCrossRefGoogle Scholar
  83. 83.
    Tunici P, Schiaffonati L, Rabellotti E, Tiberio L, Perin A, Sessa A (1999) In vivo modulation of 73 kDa heat shock cognate and 78 kDa glucose-regulating protein gene expression in rat liver and brain by ethanol. Alcoholism Clin Exp Res 23(12):1861–1867CrossRefGoogle Scholar
  84. 84.
    Borges JC, Ramos CH (2005) Protein folding assisted by chaperones. Prot Pept Lett 12(3):257–261CrossRefGoogle Scholar
  85. 85.
    Verghese L, Abrams J, Wang Y, Morano KA (2012) Biology of the heat shock response and protein chaperones: budding yeast (Saccharomyces cerevisiae) as a model system. Microbiol Mol Biol Rev 76(2):115–158. PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Geuens T, Bouhy D, Timmermann V (2016) The hnRNP family: insights into their role in health and disease. Hum Genet 135(8):851–867. PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Šerý O, Sultana N, Kashem MA, Pow DV, Balcar VJ (2015) GLAST but not least–distribution, function, genetics and epigenetics of L-glutamate transport inbrain–focus on GLAST/EAAT1. Neurochem Res 40(12):2461–2472. PubMedCrossRefGoogle Scholar
  88. 88.
    Alshehri FS, Althobaiti YS, Sari Y (2017) Effects of administered athanol and amphetamine on glial glutamate transporters in rat striatum and Hippocampus. J Mol Neurosci 61(3):343–350 doi:_10.1007/s12031-016-0859-8PubMedCrossRefGoogle Scholar
  89. 89.
    Kryger R, Wilce PA (2010) The effects of alcoholism on the human basolateral amygdala. Neuroscience 167(2):361–371. PubMedCrossRefGoogle Scholar
  90. 90.
    Lee A, Pow DV (2010) Astrocytes: Glutamate transport and alternate splicing of transporters. Int J Biochem Cell Biol 42(12):1901–1906PubMedCrossRefGoogle Scholar
  91. 91.
    Rimondini R, Arlinde C, Sommer W, Heilig M (2002) Long-lasting increase in voluntary ethanol consumption and transcriptional regulaton in the rat brain after intermittent exposure to alcohol. FASEB J 16(1):27–35PubMedCrossRefGoogle Scholar
  92. 92.
    Flatscher-Bader T, Wilce PA (2005) Impact of alcohol abuse on protein expression of midkine and excitatory amino acid transporter 1 in the human prefrontal cortex. Alcoholism Clin Exp Res 32(10):1849–1858CrossRefGoogle Scholar
  93. 93.
    Anantha RW, Alcivar AL, Ma J, Cai H, Simhadri S, Ule J, Konig J, Xia B (2013) Requirement of heterogeneous nuclear ribonucleoprotein C for BRCA gene expression and homologous recombination. PloS ONE 8(4)::e61368. CrossRefGoogle Scholar
  94. 94.
    Zhang Y, Zhang YL, Feng C, Wu YT, Liu AX, Sheng JZ, Cai J, Huang HF (2008) Comparative proteomic analysis of human placenta derived from assisted reproductive technology. Proteomics 8(20):4344–4356. PubMedCrossRefGoogle Scholar
  95. 95.
    Sari Y, Zhang M, Mechref Y (2010) Differential expression of proteins in fetal brains of alcohol-treated prenatally C57BL/6 mice: a proteomic investigation. Electrophoresis 31(3):483–496. PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Umate P, Tuteja N, Tuteja R (2011) Genome-wide comprehensive analysis of human helicases. Comm Integr Biol 4(1):118–137. CrossRefGoogle Scholar
  97. 97.
    Schwer B, Meszaros T (2000) RNA helicase dynamics in pre-mRNA splicing. Eur Mol Biol J 19(23):6582–6591CrossRefGoogle Scholar
  98. 98.
    Kedde M, Agami R (2008) Interplay between microRNAs and RNA-binding proteins determines developmental processes. Cell Cycle 7(7):899–903PubMedCrossRefGoogle Scholar
  99. 99.
    Youngren KK, Coveney D, Peng X, Bhattacharya C, Schmidt LS, Nickerson ML, Lamb BT, Deng JM, Behringer RR, Capel B, Rubin EM, Nadeau JH, Matin A (2005) The Ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours. Nature 435(7040):360–364PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Zhu R, Iacovino M, Mahen E, Kyba M, Matin A (2011) Transcripts that associate with the RNA binding protein, DEAD-END (DND1), in embryonic stem (ES) cells. BMC Mol Biol 12::37CrossRefGoogle Scholar
  101. 101.
    Bhattacharya C, Aggarwal S, Zhu R, Kumar M, Zhao M, Meistrich ML, Matin A (2007) The mouse dead-end gene isoform alpha is necessary for germ cell and embryonic viability. Biochem Biophys Res Comm 355(1):194–199PubMedCrossRefGoogle Scholar
  102. 102.
    Colombo E, Bonetti P, Lazzerini Denchi E, Martinelli P, Zamponi R, Marine JC, Helin K, Falini B, Pelicci PG (2005) Nucleophosmin is required for DNA integrity and p19Arf protein stability. Mol Cell Biol 25(20):8874–8886PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Okuwaki M, Matsumoto K, Tsujimoto M, Nagata K (2001) Function of nucleophosmin/B23, a nuceleolar acidic protein, as a histone chaperone. FEBS Lett 506(3):272–276PubMedCrossRefGoogle Scholar
  104. 104.
    Abe M, Lin J, Nagata K, Okuwaki M (2018) Selective regulation of type II interferon-inducible genes by NPM1/nucleophosmin. FEBS Lett 595(2):244–255. CrossRefGoogle Scholar
  105. 105.
    Chiarella S, De Cola A, Scaglione GL, Carletti E, Graziano V, Barcaroli D, Lo Sterzo C, Di Matteo A, Di Ilio C, Falini B, Arcovito A, De Laurenzi V, Federici L (2013) Nucleophosmin mutations alter its nucleolar localization by impairing G-quadruplex binding at ribosomal DNA. Nucl Acids Res 41(5):3228–3239. PubMedCrossRefGoogle Scholar
  106. 106.
    Lill NL, Grossman SR, Ginsberg D, DiCaprio J, Livingston DM (1997) Binding and modulation of p53 by p300/CBP coactivators. Nature 387:823–827PubMedCrossRefGoogle Scholar
  107. 107.
    Kasper LH, Thomas MC, Zambetti GP, Brindle PK (2011) Double null cells reveal that CBP and p300 are dispensable for p53 targets p21 and Mdm2 but variably required for target genes of other signaling pathways. Cell Cycle 10(2):212–221PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Abbas T, Dutta A (2009) P21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 9(6):400–414. PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Sikker W Jr, Liu F, Rainosk SW, Patterson TA, Sadovova N, Hanig JP, Paule MG, Wang C (2015) Ketamine-induced toxicity in neurons differntiated from neural stem cells. Mol Neurobiol 52:959–969 CrossRefGoogle Scholar
  110. 110.
    Wang JW, Cheng WW, Xu T, Yang ZY (2015) Propofol nduces apoptosis and inhibits the proliferation of rat embryonic stem cells via gamma-aminobutyric acid type A receptor. Genet Mol Res 14(4):14920–14928 doi. org/PubMedCrossRefGoogle Scholar
  111. 111.
    Qiu J, Shi P, Mao W, Zhao Y, Liu W, Wang Y (2015) Effect of apoptosis in neural stem cells treated with sevoflurane. BMC Anesthesiology 15:25. PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mohammed A. Kashem
    • 1
  • Nilufa Sultana
    • 1
  • Vladimir J. Balcar
    • 1
    Email author
  1. 1.Laboratory of Neurochemistry, Bosch Institute and Discipline of Anatomy and Histology, School of Medical Sciences, Sydney Medical SchoolThe University of SydneySydneyAustralia

Personalised recommendations