Effect of Gas6 on secretory phospholipase A 2-IIA-induced apoptosis in cortical neurons

Abstract

Gas6, a product of the growth-arrest-specific gene 6, protects cortical neurons from amyloid β protein (Aβ)-induced apoptosis. Neuronal apoptosis is also caused by human group IIA secretory phospholipase A 2 (sPLA 2-IIA), which is expressed in the cerebral cortex after brain ischemia. sPLA 2-IIA induces Ca 2+ influx via L-type voltage-sensitive calcium channels (L-VSCCs), leading to its neurotoxicity. In the present study, we investigated effects of Gas6 on sPLA 2-IIA-induced cell death in primary cultures of rat cortical neurons. sPLA 2-IIA caused neuronal cell death in a concentration- and time-dependent manner. Gas6 significantly prevented neurons from sPLA 2-IIA-induced cell death. Gas6 suppressed sPLA 2-IIA-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA. Prior to cell death, sPLA 2-IIA increased the influx of Ca 2+ into neurons through L-VSCCs. Gas6 significantly inhibited the sPLA 2-IIA-induced Ca 2+ influx. The blocker of L-VSCCs also suppressed sPLA 2-IIA-induced neuronal cell death. The cortical cultures contained few non-neuronal cells, indicating that Gas6 affected the survival of neurons directly, but not indirectly via non-neuronal cells. In conclusion, we demonstrate that Gas6 rescues cortical neurons from sPLA 2-IIA-induced apoptosis. Furthermore, the present study indicates that inhibition of L-VSCC contributes to the neuroprotective effect of Gas6.