Endoplasmic Reticulum Calcium Release Engages Bax Translocation in Cortical Astrocytes

Apoptosis is a highly complex form of cell death that can be triggered by alterations in Ca2+ homeostasis. Members of the Bcl-2 family may regulate apoptosis and modulate Ca2+ distribution within intracellular compartments. Bax, a proapoptotic member of the family, is constitutively expressed and soluble in the cytosol and, under apoptotic induction, translocates to mitochondrial membranes. However, it is not clear if the intracellular Ca2+ stores and selective Ca2+ releases can modulate or control Bax translocation. The aim of this study was to investigate the relation of intracellular Ca2+ stores with Bax translocation in rat cortical astrocytes. Results show that the classical apoptotic inducer, staurosporine, caused high elevations of cytosolic Ca2+ that precede Bax translocation. On the other hand, agents that mobilize Ca2+ from endoplasmic reticulum such as noradrenaline or thapsigargin, induced Bax translocation, while mitochondrial Ca2+ release evoked by carbonyl cyanide-p-(trifluoromethoxyphenyl) hydrazone was not able to cause Bax punctation. In addition, microinjection of inositol 1,4,5- trisphosphate induced Bax translocation. Taken together, our results show that in Bax overexpressing cortical astrocytes, endoplasmic reticulum-Ca2+ release may induce Bax transactivation and specifically control apoptosis.