Influence of ER leak on resting cytoplasmic Ca2+ and receptormediated Ca2+ signalling in human macrophage

Layhadi, Janice A. and Fountain, Samuel J. (2017) Influence of ER leak on resting cytoplasmic Ca2+ and receptormediated Ca2+ signalling in human macrophage. Biochemical and Biophysical Research Communications, 487 (3). 633–639. ISSN 0006-291X

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Abstract

Mechanisms controlling endoplasmic reticulum (ER) Ca2+ homeostasis are important regulators of resting cytoplasmic Ca2+ concentration ([Ca2+]cyto) and receptor-mediated Ca2+ signalling. Here we investigate channels responsible for ER Ca2+ leak in THP-1 macrophage and human primary macrophage. In the absence of extracellular Ca2+ we employ ionomycin action at the plasma membrane to stimulate ER Ca2+ leak. Under these conditions ionomycin elevates [Ca2+]cyto revealing a Ca2+ leak response which is abolished by thapsigargin. IP3 receptors (Xestospongin C, 2-APB), ryanodine receptors (dantrolene), and translocon (anisomycin) inhibition facilitated ER Ca2+ leak in model macrophage, with translocon inhibition also reducing resting [Ca2+]cyto. In primary macrophage, translocon inhibition blocks Ca2+ leak but does not influence resting [Ca2+]cyto. We identify a role for translocon-mediated ER Ca2+ leak in receptor-mediated Ca2+ signalling in both model and primary human macrophage, whereby the Ca2+ response to ADP (P2Y receptor agonist) is augmented following anisomycin treatment. In conclusion, we demonstrate a role of ER Ca2+ leak via the translocon in controlling resting cytoplasmic Ca2+ in model macrophage and receptor-mediated Ca2+ signalling in model macrophage and primary macrophage.

Item Type: Article
Uncontrolled Keywords: endoplasmic reticulum,calcium leak,translocon,macrophage,purinergic
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: Pure Connector
Date Deposited: 13 May 2017 05:05
Last Modified: 22 Apr 2020 04:29
URI: https://ueaeprints.uea.ac.uk/id/eprint/63499
DOI: 10.1016/j.bbrc.2017.04.106

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