Neuronal apoptosis induced by endoplasmic reticulum stress.
Apoptosis is a conserved active cellular mechanism occurring under a range of physiological and pathological conditions. In the nervous system, apoptosis plays crucial roles in normal development and neuronal degenerating diseases. Various deleterious conditions, including accumulation of the mutant proteins in the endoplasmic reticulum (ER) and inhibition of ER to Golgi transport of proteins, may result in apoptosis. In this study, we examined the downstream events of apoptosis in differentiated PC 12 cells under ER stress induced by brefeldin A, an inhibitor of ER to Golgi protein transport. Activation of NF-kappaB and degradation of I-kappaB were observed within 2 hours, followed by up-regulation of GRP78 protein level in treated cells. Caspase-12 only appeared around 24 hours after brefeldin A treatment, coincident with cell nuclei fragmentation. These results suggest that neuronal apoptosis may be induced by ER stress through a NF-kappaB and caspase related pathway.
Chen
Lizhen
L
Model Animal Research Center, Institute of Molecular Medicine, Nanjing University, People's Republic of China.
Gao
Xiang
X
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D020126:Brefeldin A / Q000494:pharmacology; D053454:Caspase 12; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D018384:Oxidative Stress; D016716:PC12 Cells; D051381:Rats
D017931:DNA Primers; D016328:NF-kappa B; D020126:Brefeldin A; C506443:Casp12 protein, rat; D053454:Caspase 12; D020169:Caspases