{Reference Type}: Journal Article
{Title}: Suppression of Ca2+ oscillations by SERCA inhibition in human alveolar type 2 A549 cells: rescue by ochratoxin A but not CDN1163.
{Author}: Wu KC;Chen CY;Chuang CM;Shiao LR;Chan P;Leung YM;
{Journal}: Life Sci
{Volume}: 308
{Issue}: 0
{Year}: Nov 2022 1
{Factor}: 6.78
{DOI}: 10.1016/j.lfs.2022.120913
{Abstract}: <B>OBJECTIVE: </B>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 Ca2+-dependent surfactant secretion by neighboring type 2 cells. In this report, we studied ATP-triggered Ca2+ signaling in human alveolar type 2 A549 cells.<BR><B>METHODS: </B>Ca2+ signaling was examined using microfluorimetric measurement with fura-2 as fluorescent dye.<BR><B>RESULTS: </B>Ca2+ oscillations triggered by ATP relied on inositol 1,4,5-trisphosphate-induced Ca2+ release and store-operated Ca2+ entry. Pathological conditions such as influenza virus infection and diabetes reportedly inhibit sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA). We found that a very mild inhibition of SERCA by cyclopiazonic acid (CPA) sufficed to decrease Ca2+ oscillation frequency and the percentage of cells exhibiting Ca2+ oscillations. Ochratoxin A (OTA), an activator of SERCA, could prevent the suppressive effects by CPA. Inhibition of SERCA by hydrogen peroxide also suppressed Ca2+ 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 Ca2+.<BR><B>CONCLUSIONS: </B>Different modes of activation of SERCA may determine the outcome of rescue of Ca2+ oscillations in case of SERCA inhibition in alveolar type 2 cells.