Capacitative Ca²⁺ entry is involved in regulating soluble amyloid precursor protein (sAPPα) release mediated by muscarinic acetylcholine receptor activation in neuroblastoma SH‐SY5Y cells

Abstract

Previous studies have demonstrated that stimulation of phospholipase C-linked G-protein-coupled receptors, including muscarinic M 1 and M 3 receptors, increases the release of the soluble form of amyloid precursor protein (sAPPa) by a-secretase cleavage. In this study, we examined the involvement of capacitative Ca 2+ entry (CCE) in the regu- Slack et al. 1993Slack et al. , 1995Mills and Reiner 1999;Canet-Aviles et al. 2002). In addition, it has been suggested that other PKC-independent and Ca 2+ -dependent processes are involved in the activation of the a-secretase pathway (Buxbaum et al. 1994;Racchi et al. 1998). Ligands of receptors with intrinsic tyrosine kinase activity, including nerve growth factor and epidermal growth factor, have been also shown to increase sAPPa secretion (Mills and Reiner 1999). G-protein-coupled receptors, including phospholipase C (PLC)-coupled receptors such as muscarinic M 1 and M 3 receptor subtypes (Nitsch et al. 1992;Hung et al. 1993;Buxbaum et al. 1994;Slack et al. 1995 Abbreviations used: AD, Alzheimer's disease; 2-APB, 2-aminoethoxydiphenyl borane; APP, amyloid precursor protein; CCE, capacitative Ca 2+ entry; ER, endoplasmic reticulum; HEK, human embryonic kidney; mAChR, muscarinic acetylcholine receptor; oxoM, oxotremorine-M; PKC, protein kinase C; PLC, phospholipase C; PMA, phorbol 12-myristate 13-acetate; PS1, presenilin 1; sAPPa, soluble form of APP by a-secretase cleavage; SOCCs, store-operated Ca 2+ channels; TRP, transient receptor potential.

Nuclear Factor-κB Activated by Capacitative Ca2+ Entry Enhances Muscarinic Receptor-mediated Soluble Amyloid Precursor Protein (sAPPα) Release in SH-SY5Y Cells

“…Numerous studies have demonstrated that stimulation of phospholipase C-linked G-protein-coupled receptors, including muscarinic M1 and M3 receptors, increases the release of the sAPP␣ by ␣-secretase cleavage. The purpose of this research was to determine whether muscarinic receptor stimulation activates NF-B in neuroblastoma SH-SY5Y cells expressing abundant M3 muscarinic receptors and whether such muscarinic receptor-mediated NF-B activation is involved in sAPP␣ release and contributes to change the CCE, which our recent data (25) indicate plays an important role in the muscarinic receptor-mediated stimulation of sAPP␣ release.…”

“…Several studies have demonstrated that various transcription factors are regulated by intracellular Ca 2ϩ movement (19,21,51). We observed that extracellular Ca 2ϩ influx (CCE) via SOC, which is functionally coupled with endoplasmic reticulum Ca 2ϩ depletion, plays a key role in muscarinic receptor-mediated sAPP␣ release (25). Thus, we attempted to characterize the nature of the Ca 2ϩ influx that participates in muscarinic receptor-mediated NF-B activation by administering Ca 2ϩ channel blockers.…”

“…Moreover, in neuronal cells, the involvement of CCE in muscarinic receptor-mediated NF-B activation or vice versa is little understood. Our recent data indicated that CCE is involved in the regulation of muscarinic receptormediated sAPP␣ release (25), and we postulated that NF-B might be an important signaling molecule in the regulation of muscarinic receptormediated sAPP␣ release. Therefore, in the present study, we examined how NF-B and CCE are involved in muscarinic receptor-mediated sAPP␣ release in SH-SY5Y human neuroblastoma cells.…”

Translationally Controlled Tumor Protein Stimulates Dopamine Release from PC12 Cells via Ca2+-Independent Phospholipase A2 Pathways

“…Our data indicate that the rTCTP-induced increase in [Ca 2+ ] i was due to a Ca 2+ influx from an extracellular source rather than via voltage-gated L-type Ca 2+ channels, and that rTCTP does not mobilize Ca 2+ from intracellular stores. Thapsigargin, an inhibitor of Ca 2+ -ATPase in the membranes of ER Ca 2+ stores, is generally used to inhibit refilling of Ca 2+ stores and subsequently depleting Ca 2+ from Ca 2+ stores in various cells [15,16], including PC12 cells. When PC12 cells were exposed to 1 µM thapsigargin in a Ca 2+ -containing buffer, it caused a sustained increase in [Ca 2+ ] i , confirming that intracellular Ca 2+ stores are releasable under our experimental conditions.…”

Activation of the Human FPRL-1 Receptor Promotes Ca2+ Mobilization in U87 Astrocytoma Cells

“…They include the GABA B [27], group I metabotropic [42], chemoattractant [43], and muscarinic acetylcholine [44,45] receptors. However, the mechanism linking activated GPCRs to SOCs remains elusive.…”