2‑Aminoethoxydiphenyl Borate Perturbs Hormone Sensitive Calcium Stores and Blocks Store Operated Calcium Influx Pathways Independent of Cytoskeletal Disruption in Human A549 Lung Cancer Cells
ORCiD
0000-0001-9010-5970
Document Type
Article
Publication Title
Biochemical Pharmacology
ISSN
0006-2952
Volume
69
Issue
8
DOI
10.1016/j.bcp.2005.01.011
First Page
1177
Last Page
1186
Publication Date
4-1-2005
Abstract
Recent studies have identified novel actions for 2-aminoethoxydiphenyl borate (2-APB) in triggering calcium release and enhancing calcium influx induced by the depletion of intracellular calcium stores. In this study, we have examined the effects of 2-APB on the human lung adenocarcinoma A549 cell line, which we have previously shown displays a unique calcium influx response, when ER calcium stores are depleted by thapsigargin (TG) treatment. Here, we show that low concentrations of 2-APB failed to induce the rapid augmentation of TG-activated calcium influx previously reported for other cell types. We observed that store-operated calcium (SOC) channels in the A549 cell line exhibited short-term sensitivity to low doses of 2-APB, perhaps reflecting a delayed augmentation of SOC channel activity or the recruitment of 2-APB-insensitive SOC channels. In both intact and permeabilized cells, 2-APB effectively discharged a subset of A549 calcium pools corresponding to the hormone-sensitive intracellular calcium stores. The 2-APB-induced calcium release produced a long-lasting perturbation of the adenosine triphosphate (ATP)-releasable calcium pools, effectively uncoupling ATP-activated calcium release even, when stores are replenished with calcium. In contrast to previous reports, we found that disruption of either the actin or microtubule-based cytoskeleton failed to block the 2-APB-induced effects on calcium signaling in A549 cells. Our study describes novel cytoskeletal-independent effects of 2-APB on Ca2+-signaling pathways, revealing differentially sensitive Ca2+-influx pathways and long-term perturbation of hormone-sensitive Ca2+ stores.
Recommended Citation
Pader, S.,
Bose, D.,
Livesey, J. C.,
&
Thomas, D. W.
(2005).
2‑Aminoethoxydiphenyl Borate Perturbs Hormone Sensitive Calcium Stores and Blocks Store Operated Calcium Influx Pathways Independent of Cytoskeletal Disruption in Human A549 Lung Cancer Cells.
Biochemical Pharmacology, 69(8), 1177–1186.
DOI: 10.1016/j.bcp.2005.01.011
https://scholarlycommons.pacific.edu/phs-facarticles/202
