S100b protects IMR-32 cells against Ab(1-42) induced neurotoxicity via modulation of apoptotic genes expression
Author(s)
M. Elisabetta Clementi*,
Beatrice Sampaolese,
Doriana Triggiani,
Antonio Tiezzi,
Bruno Giardina
Affiliation(s)
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.
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.
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.
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.
Cite this paper
Clementi, M. , Sampaolese, B. , Triggiani, D. , Tiezzi, A. and Giardina, B. (2013) S100b protects IMR-32 cells against Ab(1-42) induced neurotoxicity via modulation of apoptotic genes expression. Advances in Alzheimer's Disease, 2, 99-108. doi: 10.4236/aad.2013.23013.
Clementi, M. , Sampaolese, B. , Triggiani, D. , Tiezzi, A. and Giardina, B. (2013) S100b protects IMR-32 cells against Ab(1-42) induced neurotoxicity via modulation of apoptotic genes expression. Advances in Alzheimer's Disease, 2, 99-108. doi: 10.4236/aad.2013.23013.
References
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(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. 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