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Nuclear factor-κB activated by capacitative Ca2+ entry enhances muscarinic receptor-mediated soluble amyloid precursor protein (sAPPα) release in SH-SY5Y cells

Title
Nuclear factor-κB activated by capacitative Ca2+ entry enhances muscarinic receptor-mediated soluble amyloid precursor protein (sAPPα) release in SH-SY5Y cells
Authors
Choi S.Jin H.K.Roh E.-J.Ko M.-J.Jung J.-E.Kim H.-J.
Ewha Authors
김화정최신규
SCOPUS Author ID
김화정scopus
Issue Date
2006
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
Journal of Biological Chemistry vol. 281, no. 18, pp. 12722 - 12728
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Gq/11 protein-coupled muscarinic receptors are known to regulate the release of soluble amyloid precursor protein (sAPPα) produced by α-secretase processing; however, their signaling mechanisms remain to be elucidated. It has been reported that a muscarinic agonist activates nuclear factor (NF)-κB, a transcription factor that has been shown to play an important role in the Alzheimer disease brain, and that NF-κB activation is regulated by intracellular Ca2+ level. In the present study,weinvestigated whether NF-κB activation plays a role in muscarinic receptor-mediated sAPPα release enhancement and contributes to a changed capacitative Ca2+ entry (CCE), which was suggested to be involved in the muscarinic receptor-mediated stimulation of sAPPα release. Muscarinic receptor-mediated NF-κB activation was confirmed by observing the translocation of the active subunit (p65) of NF-κB to the nucleus by the muscarinic agonist, oxotremorine M (oxoM), in SH-SY5Y neuroblastoma cells expressing muscarinic receptors that are predominantly of the M3 subtype. NF-κB activation and sAPPα release enhancement induced by oxoM were inhibited by NF-κB inhibitors, such as an NF-κB peptide inhibitor (SN50), an IκBα kinase inhibitor (BAY11-7085), a proteasome inhibitor (MG132), the inhibitor of proteasome activity and IκB phosphorylation, pyrrolidine dithiocarbamate, the novel NF-κB activation inhibitor (6-amino-4-(4-phenoxyphenylethylamino) quinazoline), and by an intracellular Ca2+ chelator (TMB-8). Furthermore, both oxoM-induced NF-κB activation and sAPPα release were antagonized by CCE inhibitors (gadolinium or SKF96365) but not by voltage-gated Ca 2+-channel blockers. On the other hand, treatment of cells with NF-κB inhibitors (SN50, BAY11-7085, MG132, or pyrrolidine dithiocarbamate) did not inhibit muscarinic receptor-mediated CCE. These findings provide evidence for the involvement of NF-κB regulated by CCE in muscarinic receptor-mediated sAPPα release enhancement. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI
10.1074/jbc.M601018200
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약학대학 > 약학과 > Journal papers
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