Suppression of Ca oscillations by SERCA inhibition in human alveolar type 2 A549 cells: rescue by ochratoxin A but not CDN1163.

AIMS

Lung type 2 alveolar cells, by secreting surfactant to lower surface tension, contribute to enhance lung compliance. Stretching, as a result of lung expansion, triggers type 1 alveolar cell to release ATP, which in turn stimulates Ca-dependent surfactant secretion by neighboring type 2 cells. In this report, we studied ATP-triggered Ca signaling in human alveolar type 2 A549 cells.

MAIN METHODS

Ca signaling was examined using microfluorimetric measurement with fura-2 as fluorescent dye.

KEY FINDINGS

Ca oscillations triggered by ATP relied on inositol 1,4,5-trisphosphate-induced Ca release and store-operated Ca entry. Pathological conditions such as influenza virus infection and diabetes reportedly inhibit sarcoplasmic/endoplasmic reticulum Ca ATPase (SERCA). We found that a very mild inhibition of SERCA by cyclopiazonic acid (CPA) sufficed to decrease Ca oscillation frequency and the percentage of cells exhibiting Ca oscillations. Ochratoxin A (OTA), an activator of SERCA, could prevent the suppressive effects by CPA. Inhibition of SERCA by hydrogen peroxide also suppressed Ca oscillations. Interestingly, hydrogen peroxide-induced inhibition was prevented by OTA but aggravated by CDN1163, an allosteric activator of SERCA. CDN1163 also had an untoward effect of releasing intracellular Ca.

SIGNIFICANCE

Different modes of activation of SERCA may determine the outcome of rescue of Ca oscillations in case of SERCA inhibition in alveolar type 2 cells.