|
Yoshida I, Monji A, Tashiro K, Nakamura K, Inoue R, Kanba S.
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.
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)).
PMID: 16481070 |
