Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells

  • Neurochem Int. 2006 Jun;48(8):696-702. doi: 10.1016/j.neuint.2005.12.012.
Ichiro Yoshida  1 ,  Akira Monji ,  Ken-ichiro Tashiro ,  Kei-ichiro Nakamura ,  Ryuji Inoue ,  Shigenobu Kanba
Affiliations
  • 1. Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
PMID: 16481070 DOI: 10.1016/j.neuint.2005.12.012
Abstract

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)).

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