Calcium Pathways in Human Neutrophils—The Extended Effects of Thapsigargin and ML-9
AbstractIn 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
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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.
Ribeiro D, Freitas M, Rocha S, Lima JLFC, Carvalho F, Fernandes E. Calcium Pathways in Human Neutrophils—The Extended Effects of Thapsigargin and ML-9. Cells. 2018; 7(11):204.Chicago/Turabian Style
Ribeiro, Daniela; Freitas, Marisa; Rocha, Sílvia; Lima, José L.F.C.; Carvalho, Félix; Fernandes, Eduarda. 2018. "Calcium Pathways in Human Neutrophils—The Extended Effects of Thapsigargin and ML-9." Cells 7, no. 11: 204.
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