S100b protects IMR-32 cells against Ab(1-42) induced neurotoxicity via modulation of apoptotic genes expression

M. Elisabetta Clementi, Beatrice Sampaolese, Doriana Triggiani, Antonio Tiezzi, Bruno Giardina

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1CNR-ICRM Institute of Chimica del Riconoscimento Molecolare.
Department for Innovation in Biological, Agro-food and Forest Systems (DIBAF), Tuscia University, Viterbo, Italy.
Institute of Biochemistry and Clinical Biochemistry, Catholic University School of Medicine, Rome, Italy.

DOI: 10.4236/aad.2013.23013                

Abstract

Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focused on identifying new protective substances that prevent or almost retard the appearance of amyloid beta (1-42)-related neurotoxic effects. In this study, human neuroblastoma cells (IMR-32) was used as system model to evaluate the protective role of S100b, a neurotrophic factor and neuronal survival protein, that is highly expressed by reactive astrocytes in close vicinity of beta-amyloid deposits, against amyloid beta (1-42)-dependent toxicity. Our results show that at nanomolar concentrations, S100b protects cells against Aβmediated cytotoxicity, as assessed by MTS vitality test. The protective mechanism seems to be related to the effect on bcl-2 (an anti-apoptotic gene) expression, which is highly down-regulated by amyloid beta (1-42) treatment, while resulted more expressed in the presence of S100b. On the contrary, Bax, a proapoptotic gene, resulted down-regulated by the treatment with S100 compared with the results obtained in the presence of amyloid beta (1-42) peptide. However, at micromolar doses, S100b is toxic for IMR-32 cells and its toxicity adds to that of the Aβpeptide, suggesting that additional molecular mechanisms may be involved in theneurotoxic process.

Keywords

S100b; Neurodegeneration; Oxidate Methionine; Apoptotic Genes Expression

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Donato, R., Cannon, BR., Sorci, G., Riuzzi, F., Hsu, K., Weber, D.J. and Geczy, C.L. (2012) Function of S100 proteins. Current Molecular Medicine, 13, 24-57.
[2]	Donato, R., Sorci, G., Riuzzi, F., Arcuri, C., Bianchi, R., Brozzi, F., Tubaro, C. and Giambanco, I. (2009) S100B’s double life: Intracellular regulator and extracellular signal. Biochimica et Biophysica Acta, 1793, 1008-1022. doi:10.1016/j.bbamcr.2008.11.009
[3]	Adami, C., Sorci, G., Blasi, E., Agneletti, A.L., Bistoni, F. and Donato, R. (2001) S100B expression in and effects on microglia. Glia, 33, 131-142. doi:10.1002/1098-1136(200102)33:2<131::AID-GLIA1012>3.0.CO;2-D
[4]	Donato, R. (2003) Intracellular and extracellular roles of S100 proteins. Microscopy Research and Technique, 60, 540-551.
[5]	Yamaguchi, F., Umeda, Y., Shimamoto, S., Tsuchiya, M., Tokumitsu, H., Tokuda, M. and Kobayashi, R. (2012) S100 proteins modulate protein phosphatase 5 function: A link between CA2+ signal transduction and protein dephosphorylation. The Journal of Biological Chemistry. 287, 13787-13798.
[6]	Ciccarelli, R., Di Iorio, P., Bruno, V., Battaglia, G., D’ Alimonte, I., D’Onofrio, M., Nicoletti, F. and Caciagli, F. (1999) Activation of A(1) adenosine or mGlu3 metabotropic glutamate receptors enhances the release of nerve growth factor and S-100beta protein from cultured astrocytes. Glia, 27, 275-281. doi:10.1002/(SICI)1098-1136(199909)27:3<275::AID-GLIA9>3.0.CO;2-0
[7]	Ahlemeyer, B., Beier, H., Semkova, I., Schaper, C., Krieglstein, J. (2000) S-100beta protects cultured neurons against glutamate-and staurosporine-induced damage and is involved in the antiapoptotic action of the 5 HT(1A)- receptor agonist, Bay x 3702. Journal of Brain Research, 858, 121-128.
[8]	Pinto, S.S., Gottfried, C., Mendez, A., Goncalves, D., Karl, J., Goncalves, C.A., Wofchuk, S. and Rodnight, R. (2000) Immunocontent and secretion of S100B in astrocyte cultures from different brain regions in relation to morphology. FEBS Letters, 486, 203-207.
[9]	Tort, A.B., Portela, L.V., da Purificacao Tavares, M., Goncalves, C.A., Netto, C., Giugliani, R. and Souza DO. (2004) Specificity and sensitivity of S100B levels in amniotic fluid for Down syndrome diagnosis. Life Sciences, 76, 379-384.
[10]	Netto, C.B., Portela, L.V., Ferreira, C.T., Kieling, C., Matte, U., Felix, T., da Silveira, T.R., Souza, DO., Goncalves, C.A. and Giugliani, R. (2005) Ontogenetic changes in serum S100B in down syndrome patients. Clinical Biochemistry, 38, 433-435. doi:10.1016/j.clinbiochem.2004.12.014
[11]	Jesse, S., Steinacker, P., Cepek, L., von Arnim, C.A., Tumani, H., Lehnert, S., Kretzschmar, H.A., Baier, M. and Otto, M. (2009) Glial fibrillary acidic protein and protein S-100B: Different concentration pattern of glial proteins in cerebrospinal fluid of patients with Alzheimer’s disease and Creutzfeldt-Jakob disease. Journal of Alzheimer’s Disease, 17, 541-51.
[12]	Chaves, M.L., Camozzato, A.L., Ferreira, E.D., Piazenski, I., Kochhann, R., Dall’Igna, O., Mazzini, G.S., Souza, DO. and Portela, L.V. (2010) Serum levels of S100B and NSE proteins in Alzheimer’s disease patients. Journal of Neuroinflammation, 27, 6.
[13]	Li, C., Zhao, R., Gao, K., Wei, Z., Yin, M.Y., Lau, L.T., Chui, D. and Hoi Yu. A.C. (2011) Astrocytes: Implications for neuroinflammatory pathogenesis of Alzheimer’s disease. Current Alzheimer Research, 8, 67-80. doi:10.2174/156720511794604543
[14]	Medeiros, R. and LaFerla, F.M. (2013) Astrocytes: Conductors of the Alzheimer disease neuroinflammatory symphony. Experimental Neurology, 239, 133-138.
[15]	Marshak, D.R., Pesce, S.A., Stanley, L.C. and Griffin, W.S. (1992) Increased S100 beta neurotrophic activity in Alzheimer’s disease temporal lobe. Neurobiology of Aging, 13, 1-7. doi:10.1016/0197-4580(92)90002-F
[16]	Mori, T., Koyama, N., Arendash, G.W., Horikoshi-Sakuraba, Y., Tan, J. and Town, T. (2010) Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer’s disease. Glia, 58, 300-314.
[17]	Casta?o, E.M., Maarouf, C.L., Wu, T., Leal, M.C., Whiteside, C.M., Lue, L.F., Kokjohn, T.A., Sabbagh, M.N., Beach, T.G. and Roher, A.E. (2012) Alzheimer disease periventricular white matter lesions exhibit specific proteomic profile alterations. Neurochemistry International, 62, 145-156.
[18]	Clementi, M.E., Pezzotti, M., Orsini, F., Sampaolese, B., Mezzogori, D., Grassi, C., Giardina, B. and Misiti, F. (2006) Alzheimer’s amyloid beta-peptide (1-42) induces cell death in human neuroblastoma via bax/bcl-2 ratio increase: An intriguing role for methionine 35. Biochemical and Biophysical Research Communications, 342, 206- 213.
[19]	Butterfield, D.A., Galvan, V., Lange, M.B., Tang, H., Sowell, R.A., Spilman, P., Fombonne, J., Gorostiza, O., Zhang, J., Sultana, R. and Bredesen, D.E. (2010) In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid beta-peptide of APP. Free Radical Biology & Medicine, 48, 136-144.
[20]	Butterfield, D.A. and Sultana, R. (2011) Methionine-35 of aβ(1-42): Importance for oxidative stress in Alzheimer disease. Journal of Amino Acids, 2011, 1-10. doi:10.4061/2011/198430
[21]	Pike, C.J., Burdick, D., Welencewicz, A.J., Glabe, C.G. and Cotman C.W. (1993) Neu-rodegeneration induced by β-amyloid peptides in vitro: The role of peptide assembly state. The Journal of Neuroscience, 13, 1676-1678.
[22]	Boland, K., Behrens, M., Choi, D., Manias, K. and Perlmutter, D.H. (1996) The serpin-enzyme complex receptor recognizes soluble, nontoxic amyloid-beta peptide but not aggregated, cytotoxic amyloid-beta peptide. The Journal of Biological Chemistry, 271, 18032-18044. doi:10.1074/jbc.271.30.18032
[23]	Cory, A.H., Owen, T.C., Barltrop, J.A. and Cory, J.G. (1991) Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. Cancer Communications, 3, 207-212.
[24]	Clementi, M.E., Marini, S., Coletta, M., Orsini, F., Giardina, B. and Misiti, F. (2005) Abeta(31-35) and Abeta(25-35) fragments of amyloid beta-protein induce cellular death through apoptotic signals: Role of the redox state of methionine-35. FEBS Letters, 579, 2913-2918.
[25]	Businaro, R., Leone, S., Fabrizi, C., Sorci, G., Donato, R., Lauro, G.M. and Fumagalli, L. (2006) S100B protects LAN-5 neuroblastoma cells against Abeta amyloid-induced neurotoxicity via RAGE engagement at low doses but increases Abeta amyloid neurotoxicity at high doses. Journal of Neuroscience Research, 83, 897-906. doi:10.1002/jnr.20785
[26]	Villarreal, A., Aviles Reyes, R.X., Angelo, M.F., Reines, A.G., Ramos, A.J. (2011) S100B alters neuronal survival and dendrite extension via RAGE-mediated NF-κB signaling. Journal of Neurochemistry, 117, 321-332. doi:10.1111/j.1471-4159.2011.07207.x
[27]	De Strooper, B. (2010) Proteases and proteolysis in Alzheimer disease: A multifactorial view on the disease process. Physiological Reviews, 90, 465-494. doi:10.1152/physrev.00023.2009
[28]	Ubhi, K. and Masliah, E. (2013) Alzheimer’s disease: Recent advances and future perspectives. Journal of Alzheimer’s Disease, 33, S185-194.
[29]	Schweers, O., Sch?nbrunn-Hanebeck, E., Marx, A. and Mandelkow, E. (1994) Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure. The Journal of Biological Chemistry, 269, 24290-24297,
[30]	Wahlstr?m, A., Hugonin, L., Perálva-rez-Marín, A., Jarvet, J. and Gr?slund, A. (2008) Secondary structure conversions of Alzheimer’s Abeta(1-40) peptide induced by membrane-mimicking detergents. FEBS J, 275, 117-128. doi:10.1111/j.1742-4658.2008.06643.x
[31]	Manzoni, C., Colombo, L., Bigini, P., Diana, V., Cagnotto, A., Messa, M., Lupi, M., Bonetto, V., Pignataro, M., Airoldi, C., Sironi, E., Williams, A. and Salmona, M. (2011) The molecular assembly of amyloid aβ controls its neurotoxicity and binding to cellular proteins. PLoS One, 6, e24909. doi:10.1371/journal.pone.0024909
[32]	Butterfield, A., Swomley, A.M. and Sultana, R. (2012) Amyloid β-peptide 1-42-induced oxidative stress in Alzheimer disease: Importance in disease pathogenesis and progression. Antioxidants & Redox Signaling, 18, 1-55.
[33]	Butterfield, D.A. (2003) Amyloid beta-peptide [1-42]- associated free radical-induced oxidative stress and neurodegeneration in Alzheimer’s disease brain: Mechanisms and consequences. Current Medicinal Chemistry, 10, 2651-2659. doi:10.2174/0929867033456422
[34]	Butterfield, D.A., Perluigi, M. and Sultana, R. (2006) “Oxidative stress in Alzheimer’s disease brain: New insights from redox proteomics. European Journal of Pharmacology, 545, 39-50. doi:10.1016/j.ejphar.2006.06.026
[35]	Sultana, R. and Butter-field, D.A. (2013) Oxidative modification of brain proteins in Alzheimer’s disease: Perspective on future studies based on results of redox pro- teomics studies. Journal of Alzheimer’s Disease, 33, 243-251.
[36]	Butterfield, D.A. and Bush, A.I. (2004) Alzheimer’s amyloid beta-peptide (1-42): Involvement of methionine residue 35 in the oxidative stress and neurotoxicity properties of this peptide. Neurobiology of Aging, 25, 563-568. doi:10.1016/j.neurobiolaging.2003.12.027
[37]	Misiti, F., Clementi, M.E. and Giardina, B. (2010) Oxidation of methio-nine 35 reduces toxicity of the amyloid beta-peptide(1-42) in neuroblastoma cells (IMR-32) via enzyme methionine sulfoxide reductase A expression and function. Neurochemistry International, 56, 597-602. doi:10.1016/j.neuint.2010.01.002
[38]	Naslund, J., Schierhorn, A., Hellman, U., Lannfelt, L., Roses, A.D., Tjernberg, L.O., Silberring, J., Gandy, S.E., Winblad, B. and Greengard, P. (1994) Relative abundance of Alzheimer A beta amyloid peptide variants in Alzheimer disease and normal aging. Proceedings of the National Academy of Sciences of the United States of America, 91, 8378-8382. doi:10.1073/pnas.91.18.8378
[39]	Kuo, Y.M., Kokjohn, T.A., Beach, T.G., Sue, L.I., Brune, D., Lopez, J.C., Kalback, W.M., Abramowski, D., Sturchler-Pierrat, C., Staufenbiel, M. and Roher, A.E. (2001) Comparative analysis of amyloid-beta chemical structure and amyloid plaque morphology of transgenic mouse and Alzheimer’s disease brains. The Journal of Biological Chemistry, 276, 12991-12998. doi:10.1074/jbc.M007859200
[40]	Butterfield, D.A., Galvan, V., Lange, M.B., Tang, H., Sowell, R.A., Spilman, P., Fombonne, J., Gorostiza, O., Zhang, J., Sultana, R. and Bredesen, D.E. (2010) In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid beta-peptide of APP. Free Radical Biology and Medicine, 48, 136-144. doi:10.1016/j.freeradbiomed.2009.10.035
[41]	Johansson, A.S., Bergquist, J., Volbracht, C., Paivio, A., Leist, M., Lannfelt, L. and Westlind-Danielsson, A. (2007) Attenuated amyloid-beta aggregation and neurotoxicity owing to methionine oxidation. Neuroreport, 18, 559-563. doi:10.1097/WNR.0b013e3280b07c21?
[42]	Parihar, M.S. and Hemnani, T. (2004) Alzheimer’s disease pathogenesis and therapeutic interventions. Journal of Clinical Neuroscience, 11, 456-467. doi:10.1016/j.jocn.2003.12.007
[43]	Kumar, S., Okello, E.J. and Harris, J.R. (2012) Experimental inhibition of fibrillo-genesis and neurotoxicity by amyloid-beta (Aβ) and other disease-related peptides/ proteins by plant extracts and herbal compounds. Sub- cellular Biochemistry, 65, 295-326. doi:10.1007/978-94-007-5416-4_13
[44]	Vassallo, N. and Scerri, C. (2012) Mediterranean diet and dementia of the Alzheimer type. Current Aging Science, 6, 150-162.
[45]	Kuwana, T. and Newmeyer, D.D. (2003) Bcl-2-family proteins and the role of mitochondria in apoptosis. Current Opinion in Cell Biology, 15, 691-699. doi:10.1016/j.ceb.2003.10.004
[46]	Murphy, K.M., Ranga-nathan, V., Farnsworth, M.L., Kavallaris, M. and Lock, R.B. (2000) Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death & Differentiation, 7, 102-111. doi:10.1038/sj.cdd.4400597
[47]	Budihardjo, I., Oliver, H., Lutter, M., Luo, X. and Wang, X. (1999) Biochemical pathways of caspase activation during apoptosis. Annual Review of Cell and Developmental Biology, 15, 269-290. doi:10.1146/annurev.cellbio.15.1.269
[48]	Fesik, S.W. and Shi, Y. (2001) Controlling the caspases. Science, 294, 1477-1478. doi:10.1126/science.1062236
[49]	Yan, S.D., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., Slattery, T., Zhao, L., Nagashima, M., Morser, J., Migheli, A., Nawroth, P., Stern, D. and Schmidt, A.M. (1996) RAGE and amyloid-beta peptide neurotoxicity in Alzheimer’s disease. Nature, 382, 685-691. doi:10.1038/382685a0
[50]	Hofmann, M.A., Drury, S., Fu, C., Qu, W., Taguchi, A., Lu, Y., Avila, C., Kambham, N., Bierhaus, A., Nawroth, P., Neurath, M.F., Slattery, T., Beach, D., McClary, J., Nagashima, M., Morser, J., Stern, D. and Schmidt, A.M. (1999) RAGE mediates a novel proinflammatory axis: A central cell surface receptor for S100/calgranulin polypeptides. Cell, 97, 889-901. doi:10.1016/S0092-8674(00)80801-6
[51]	Meneghini, V., Bortolotto, V., Francese, M.T., Dellarole, A., Carraro, L., Terzieva, S. and Grilli, M. (2013) Highmobility group box-1 protein and β-amyloid oligomers promote neuronal differentiation of adult hippocampal neural progenitors via receptor for advanced glycation end products/nuclear factor-κB axis: Relevance for Alzheimer’s disease. The Journal of Neuroscience, 33, 6047- 6059. doi:10.1523/JNEUROSCI.2052-12.2013
[52]	Sathe, K., Maetzler, W., Lang, J.D., Mounsey, R.B., Fleckenstein, C., Martin, H.L., Schulte, C., Mustafa, S., Synofzik, M., Vukovic, Z., Itohara, S., Berg, D. and Teismann, P. (2012) S100B is increased in Parkinson’s disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-α pathway. Brain, 135, 3336-3347. doi:10.1093/brain/aws250
[53]	Slowik, A., Merres, J., Elfgen, A., Jansen, S., Mohr, F., Wruck, C.J., Pufe, T. and Brandenburg, L.O. (2012) Involvement of formyl peptide receptors in receptor for advanced glycation end products (RAGE)—And amyloid beta 1-42-induced signal transduction in glial cells. Molecular Neurodegeneration, 7, 55.