Alteration of Mitochondrial Ca2+ Fluxes by Kaempferol and CGP-37157 Regulates Ca2+ Oscillations in Human Alveolar...

Mitochondria participate in regulating cytosolic Ca2+ signaling by their Ca2+ handling via mitochondrial Ca2+ uniporter (MCU) and mitochondrial Na+/Ca2+ exchanger (mitoNCX). In this study, we examined how agonist-triggered cytosolic Ca2+ oscillations in human alveolar type 2 A549 cells were affected by an MCU inhibitor (MCU-i4), MCU activator (kaempferol) and mitoNCX inhibitor (CGP-37157). Whilst inhibition of MCU did not significantly repress Ca2+ oscillations, MCU activation by kaempferol considerably dampened oscillatory activities. Inhibition of mitochondrial Ca2+ efflux by CGP-37157 also suppressed Ca2+ oscillations; the suppressive effects of kaempferol and CGP 37157 were not additive. Both kaempferol and CGP-37157 caused a rise in mitochondrial matrix Ca2+ level, but their effects were not additive. Taken together, our results suggest Ca2+ oscillations in alveolar type 2 A549 cells were regulated by stimulating Ca2+ uptake into, and preventing Ca2+ efflux from, the mitochondria, with both cases resulting in disturbed Ca2+ traffic and Ca2+ accumulation in the mitochondrial matrix. Key words Mitochondria " Ca2+ oscillations " Mitochondrial Ca2+ uniporter " Mitochondrial Na+/Ca2+ exchanger " A549 cells.