Gene expression during ER stress–induced apoptosis in neurons induction of the BH3-only protein Bbc3/PUMA and activation of the mitochondrial apoptosis pathway

ndoplasmic reticulum (ER) stress has been implicated in the pathogenesis of ischemic and neurodegenerative disorders. Treatment of human SH-SY5Y neuroblastoma cells with tunicamycin, an inhibitor of protein glycosylation, rapidly induced the expression of target genes of the unfolded protein response. However, prolonged treatment also triggered a delayed, caspase-dependent cell death. Microarray analysis of gene expression changes during tunicamycininduced apoptosis revealed that the Bcl-2 homology domain 3-only family member, Bcl-2 binding component 3/p53 upregulated modulator of apoptosis ( Bbc3/PUMA ), was the most strongly induced pro-apoptotic gene. Expression of