Endoplasmic Reticulum Calcium Release Engages Bax Translocation in Cortical Astrocytes

Abstract

Apoptosis is a highly complex form of cell death that can be triggered by alterations in Ca(2+) homeostasis. Members of the Bcl-2 family may regulate apoptosis and modulate Ca(2+) 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 Ca(2+) stores and selective Ca(2+) releases can modulate or control Bax translocation. The aim of this study was to investigate the relation of intracellular Ca(2+) stores with Bax translocation in rat cortical astrocytes. Results show that the classical apoptotic inducer, staurosporine, caused high elevations of cytosolic Ca(2+) that precede Bax translocation. On the other hand, agents that mobilize Ca(2+) from endoplasmic reticulum such as noradrenaline or thapsigargin, induced Bax translocation, while mitochondrial Ca(2+) 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-Ca(2+) release may induce Bax transactivation and specifically control apoptosis.

TRAP1 and the proteasome regulatory particle TBP7/Rpt3 interact in the endoplasmic reticulum and control cellular ubiquitination of specific mitochondrial proteins

“…In order to induce protein misfolding in the ER, we induced ER stress by using thapsigargin (TG), a well-known agent that mobilizes Ca 2 þ from the ER. 23 As a marker of ER stress we analyzed the expression of BiP/Grp78, a major ER chaperone protein essential for protein quality control in the ER, as well as a central regulator of the UPR. 24 Figure 2 shows that BiP mRNA expression is strongly increased, upon TG treatment, in TRAP1-interfered cells as compared with the respective control (Figures 2a and b).…”

Endoplasmic Reticulum-Targeted Aggregation-Induced Emission Luminogen for Synergetic Tumor Ablation with Glibenclamide

“…Interestingly, light irradiation further potentiated the efflux of Ca 2+ from the ER in the presence of TPA-DMPy (Figure E), which was consistent with the cytotoxicity tests (Figure B,D). More importantly, compared to three identified compounds, tetrandrine, thapsigargin, and curcumin, − TPA-DMPy induced a higher efflux of Ca 2+ from ER (Figure E).…”

Apoptosis induced by Aβ25–35 peptide is Ca2+‐IP3 signaling‐dependent in murine astrocytes

“…Our previous work supported the conclusion that alterations in intracellular ER Ca 2+ storage and the selective activation of IP 3 Rs were critical issues in astrocyte cell death (Morales et al ., ; Smaili et al ., ), where Ca 2+ released from IP 3 R selectively induced astrocyte Bax translocation. Indeed, our present results showed that Aβ induces apoptotic cell death in cortical astrocytes in the presence of increased Bax expression and its translocation.…”