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Phenotype-dependent susceptibility of cholinergic neuroblastoma cells to neurotoxic inputs

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Abstract

A preferential loss of brain cholinergic neurons in the course of Alzheimer's disease and other encephalopathies is accompanied by a proportional impairment of acetyl-CoA synthesizing capacity in affected brains. Particular susceptibility of cholinergic neurons to neurodegeneration might results from insufficient supply of acetyl-CoA for energy production and acetylcholine synthesis in these conditions. Exposure of SN56 cholinergic neuroblastoma cells to dibutyryl cAMP and retinoic acid for 3 days caused their morphologic differentiation along with the increase in choline acetyltransferase activity, acetylcholine content and release, calcium content, and the expression of p75 neurotrophin receptors. Acetyl-CoA content correlated inversely with choline acetyltransferase activity in different lines of SN56 cells. In differentiated cells, aluminum (1 mM), amyloid β25–35 (0.001 mM), and sodium nitroprusside (1 mM), caused much greater decrease of pyruvate dehydrogenase and choline acetyltransferase activities and cell viability than in nondifferentiated ones. Aluminum (1 mM) aggravated suppressory effects of amyloid β on choline acetyltransferase and pyruvate dehydrogenase activities and viability of differentiated cells. Similar additive inhibitory effects were observed upon combined exposure of differentiated cells to sodium nitroprusside and amyloid β25–35. None or much smaller suppressory effects of these neurotoxins were observed in nondifferentiated cells. Increase in the fraction of nonviable differentiated cells positively correlated with losses of choline acetyltransferase, pyruvate dehydrogenase activities, and cytoplasmic cytochrome c content in different neurotoxic conditions. These data indicate that highly differentiated cholinergic neurons may be more susceptible to aluminum and other neurotoxins than the nondifferentiated ones due to relative shortage of acetyl-CoA, increased content of Ca2+, and expression of p75 receptors, yielding increase in cytoplasmic cytochrome c and subsequently grater rate of death of the former ones.

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Acknowledgments

This work was supported by Ministry of Research and Informatization project 2 P05A 02626 and Medical University of Gdańsk project St-57. Authors thank Dr J.K. Blusztajn for SN56 cells.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Medical University of Gdańsk, Gdańsk, 80-211, Poland

    A. Szutowicz, H. Bielarczyk, S. Gul, A. Ronowska & A. Jankowska-Kulawy

  2. Department of Molecular Medicine, Medical University of Gdańsk, Gdańsk, Poland

    T. Pawełczyk

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  1. A. Szutowicz
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  2. H. Bielarczyk
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  3. S. Gul
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  4. A. Ronowska
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  5. T. Pawełczyk
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  6. A. Jankowska-Kulawy
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Correspondence to A. Szutowicz.

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Szutowicz, A., Bielarczyk, H., Gul, S. et al. Phenotype-dependent susceptibility of cholinergic neuroblastoma cells to neurotoxic inputs. Metab Brain Dis 21, 143–155 (2006). https://doi.org/10.1007/s11011-006-9007-4

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  • DOI: https://doi.org/10.1007/s11011-006-9007-4

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