PMID- 16481070 OWN - NLM STAT- MEDLINE DCOM- 20060725 LR - 20220311 IS - 0197-0186 (Print) IS - 0197-0186 (Linking) VI - 48 IP - 8 DP - 2006 Jun TI - Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells. PG - 696-702 AB - The mechanisms of intracellular calcium store depletion and store-related Ca(2+) dysregulation in relation to apoptotic cell death in PC12 cells were investigated at physiological temperatures with a leak-resistant fluorescent indicator dye Fura-PE3/AM 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 Ca(2+) by BAPTA/AM (50 microM), or La(3+) (100 microM) enhanced while dantrolene (100 microM) 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 Ca(2+) 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 Ca(2+) concentrations ([Ca(2+)](i)). FAU - Yoshida, Ichiro AU - Yoshida I AD - Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan. FAU - Monji, Akira AU - Monji A FAU - Tashiro, Ken-ichiro AU - Tashiro K FAU - Nakamura, Kei-ichiro AU - Nakamura K FAU - Inoue, Ryuji AU - Inoue R FAU - Kanba, Shigenobu AU - Kanba S LA - eng PT - Journal Article DEP - 20060214 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Chelating Agents) RN - 0 (Enzyme Inhibitors) RN - 0 (GRP78 protein, rat) RN - 0 (Heat-Shock Proteins) RN - 0 (Molecular Chaperones) RN - 0 (Muscle Relaxants, Central) RN - 0 (fura-PE3) RN - 67526-95-8 (Thapsigargin) RN - 6I3K30563S (Lanthanum) RN - F64QU97QCR (Dantrolene) RN - SY7Q814VUP (Calcium) RN - TSN3DL106G (Fura-2) SB - IM MH - Animals MH - Apoptosis/drug effects/*physiology MH - Calcium/*metabolism MH - Calcium Signaling/*drug effects/physiology MH - Chelating Agents/pharmacology MH - Dantrolene/pharmacology MH - Endoplasmic Reticulum/drug effects/*metabolism MH - Enzyme Inhibitors/pharmacology MH - Fura-2/analogs & derivatives MH - Heat-Shock Proteins/drug effects/metabolism MH - Homeostasis/drug effects/physiology MH - Intracellular Fluid/drug effects/metabolism MH - Lanthanum/pharmacology MH - Molecular Chaperones/drug effects/metabolism MH - Muscle Relaxants, Central/pharmacology MH - Nerve Degeneration/metabolism/physiopathology MH - Neurons/drug effects/*metabolism MH - PC12 Cells MH - Rats MH - Stress, Physiological/chemically induced/*metabolism/physiopathology MH - Thapsigargin/pharmacology EDAT- 2006/02/17 09:00 MHDA- 2006/07/26 09:00 CRDT- 2006/02/17 09:00 PHST- 2005/12/13 00:00 [received] PHST- 2005/12/13 00:00 [accepted] PHST- 2006/02/17 09:00 [pubmed] PHST- 2006/07/26 09:00 [medline] PHST- 2006/02/17 09:00 [entrez] AID - S0197-0186(06)00018-0 [pii] AID - 10.1016/j.neuint.2005.12.012 [doi] PST - ppublish SO - Neurochem Int. 2006 Jun;48(8):696-702. doi: 10.1016/j.neuint.2005.12.012. Epub 2006 Feb 14.