Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 48, Issue 8, Pages 696-702Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2005.12.012
Keywords
thapsigargin; calcium homeostasis; apoptosis; cell death; PC12 cells
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The mechanisms of intracellular calcium store depletion and store-related Ca2+ dysregulationin relation to apoptotic cell death in PC12 cells were investigated at physiological temperatures with a leak-resistant fluorescent indicator dye Fura-PENAM by a cooled CCD imaging analysis system. Electron microscopic observations have shown thapsigargin (TG; 100 nM)-induced apoptosis in PC12 cells. Thorough starvation of stored Ca2+ by BAPTA/AM (50 mu M), or La3+ (100 mu M) enhanced while dantrolene (100 mu M) attenuated the TG-induced apoptosis by preventing a calcium release from internal stores. An immunoblotting analysis revealed an enhanced expression of GRP78, the hallmark of endoplasmic reticulum (ER) stress when cells were treated by TG along with BAPTA/AM. These results indicate that the depletion of the intracellular Ca2+ stores itself induces the ER stress and apoptosis in PC12 cells without any involvement of the capacitative calcium entry (CCE) or a sustained elevation of intracellular Ca2+ concentrations ([Ca2+](i)). (c) 2006 Elsevier Ltd. All rights reserved.
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