α-Synuclein modulation of Ca2+ signaling in human neuroblastoma (SH-SY5Y) cells

Hettiarachchi, Nishani T. and Parker, Andrew and Dallas, Mark L. and Pennington, Kyla and Hung, Chao-Chun and Pearson, Hugh A . and Boyle, John P. and Robinson, Philip and Peers, Chris (2009) α-Synuclein modulation of Ca2+ signaling in human neuroblastoma (SH-SY5Y) cells. Journal of Neurochemistry, 111 (5). pp. 1192-1201. ISSN 0022-3042

Full content URL: http://onlinelibrary.wiley.com/doi/10.1111/j.1471-...

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α-Synuclein modulation of Ca2+ signaling in human neuroblastoma (SH-SY5Y) cells

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Abstract

Parkinson’s disease (PD) is characterized in part by the presence of α-synuclein (α-syn) rich intracellular inclusions (Lewy bodies). Mutations and multiplication of the α-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 α-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 α-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 α-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 α-synuclein. However, only WT α-syn transfected cells displayed significantly impaired viability. Our findings suggest that α-syn regulates Ca2+ entry pathways and, consequently, that abnormal α-syn levels may promote neuronal damage through dysregulation of Ca2+ homeostasis.

Additional Information:Article first published online: 5 OCT 2009
Keywords:Ca2+ channel, Ca2+ signaling, neuroblastoma, Parkinson’s disease, SH-SY5Y, a-synuclein
Subjects:C Biological Sciences > C800 Psychology
C Biological Sciences > C860 Neuropsychology
Divisions:College of Social Science > School of Psychology
ID Code:9295
Deposited On:02 May 2013 14:53

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