Journal
MOLECULAR BRAIN RESEARCH
Volume 109, Issue 1-2, Pages 233-238Publisher
ELSEVIER
DOI: 10.1016/S0169-328X(02)00582-X
Keywords
ER stress; eIF2 alpha; Bcl-2 family; caspases; Akt
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The mechanism of endoplasmic reticulum (ER)-mediated apoptosis in neurons was examined. Using primary cortical neurons, we show that nordihydroguaiaretic acid (NDGA) and brefeldin A (BFA), two ER stressors, induce early ER stress as shown by Western blotting of the eukaryotic initiation factor-2alpha (elF2a), an ER stress marker. This event was associated with an enhancement of neuronal apoptosis as demonstrated by the time-dependent increase in caspase-3 activity and by nuclear fragmentation. The study of the apoptotic signaling showed the translocation of cytochrome c from the mitochondrial matrix to the cytosol. Further evaluation of the apoptotic process revealed that NDGA and BFA induced a rapid dephosphorylation of BAD and decrease expression of Bcl-2. Altogether, our results indicate that neuronal ER stress is associated with an apoptotic cascade involving the mitochondria. (C) 2002 Elsevier Science B.V. All rights reserved.
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