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Alpha-synuclein modulation of Ca2+ signaling in human neuroblastoma (SH-SY5Y) cells

Hettiarachchi, N. T., Parker, A., Dallas, M. L., Pennington, K., Hung, C.-C., Pearson, H. A., Boyle, J. P., Robinson, P. and Peers, C. (2009) Alpha-synuclein modulation of Ca2+ signaling in human neuroblastoma (SH-SY5Y) cells. Journal of Neurochemistry, 111 (5). pp. 1192-1201. ISSN 0022-3042

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To link to this item DOI: 10.1111/j.1471-4159.2009.06411.x

Abstract/Summary

Parkinson's disease (PD) is characterized in part by the presence of alpha-synuclein (alpha-syn) rich intracellular inclusions (Lewy bodies). Mutations and multiplication of the alpha-synuclein gene (SNCA) are associated with familial PD. Since Ca2+ dyshomeostasis may play an important role in the pathogenesis of PD, we used fluorimetry in fura-2 loaded SH-SY5Y cells to monitor Ca2+ homeostasis in cells stably transfected with either wild-type alpha-syn, the A53T mutant form, the S129D phosphomimetic mutant or with empty vector (which served as control). Voltage-gated Ca2+ influx evoked by exposure of cells to 50 mM K+ was enhanced in cells expressing all three forms of alpha-syn, an effect which was due specifically to increased Ca2+ entry via L-type Ca2+ channels. Mobilization of Ca2+ by muscarine was not strikingly modified by any of the alpha-syn forms, but they all reduced capacitative Ca2+ entry following store depletion caused either by muscarine or thapsigargin. Emptying of stores with cyclopiazonic acid caused similar rises of [Ca2+](i) in all cells tested (with the exception of the S129D mutant), and mitochondrial Ca2+ content was unaffected by any form of alpha-synuclein. However, only WT alpha-syn transfected cells displayed significantly impaired viability. Our findings suggest that alpha-syn regulates Ca2+ entry pathways and, consequently, that abnormal alpha-syn levels may promote neuronal damage through dysregulation of Ca2+ homeostasis.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy
No Reading authors. Back catalogue items
ID Code:30345
Uncontrolled Keywords:Ca2+ channel; Ca2+ signaling; neuroblastoma; Parkinson’s disease; SH-SY5Y; alpha-synuclein
Publisher:Wiley-Blackwell

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