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Cells 2018, 7(11), 204; https://doi.org/10.3390/cells7110204

Calcium Pathways in Human Neutrophils—The Extended Effects of Thapsigargin and ML-9

1
LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
2
UCIBIO, REQUIMTE, Toxicology Department, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
*
Authors to whom correspondence should be addressed.
Received: 3 October 2018 / Revised: 23 October 2018 / Accepted: 31 October 2018 / Published: 9 November 2018
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Abstract

In neutrophils, intracellular Ca2+ levels are regulated by several transporters and pathways, namely SERCA [sarco(endo)plasmic reticulum Ca2+-ATPase], SOCE (store-operated calcium entry), and ROCE (receptor-operated calcium entry). However, the exact mechanisms involved in the communication among these transporters are still unclear. In the present study, thapsigargin, an irreversible inhibitor of SERCA, and ML-9, a broadly used SOCE inhibitor, were applied in human neutrophils to better understand their effects on Ca2+ pathways in these important cells of the immune system. The thapsigargin and ML-9 effects in the intracellular free Ca2+ flux were evaluated in freshly isolated human neutrophils, using a microplate reader for monitoring fluorimetric kinetic readings. The obtained results corroborate the general thapsigargin-induced intracellular pattern of Ca2+ fluctuation, but it was also observed a much more extended effect in time and a clear sustained increase of Ca2+ levels due to its influx by SOCE. Moreover, it was obvious that ML-9 enhanced the thapsigargin-induced emptying of the internal stores. Indeed, ML-9 does not have this effect by itself, which indicates that, in neutrophils, thapsigargin does not act only on the influx by SOCE, but also by other Ca2+ pathways, that, in the future, should be further explored. View Full-Text
Keywords: human neutrophils; calcium; thapsigargin; sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA); 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) human neutrophils; calcium; thapsigargin; sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA); 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Ribeiro, D.; Freitas, M.; Rocha, S.; Lima, J.L.F.C.; Carvalho, F.; Fernandes, E. Calcium Pathways in Human Neutrophils—The Extended Effects of Thapsigargin and ML-9. Cells 2018, 7, 204.

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