title: Apoptosis induced by endoplasmic reticulum stress depends on activation of caspase-3 via caspase-12.
abstract: Recently, endoplasmic reticulum (ER) dysfunction has been implicated in neuronal death in patients with Alzheimer's disease. Treatment of human neuroblastoma cells with ER stress inducers causes apoptotic death. We confirmed that ER stress inducers specifically targeted the ER to cause apoptotic morphological changes. We also found that caspase-3, and not caspase-9 (a known mitochondrial apoptotic mediator), was mainly activated by ER stress. We generated the neuroblastoma cells that stably expressed caspase-12 and analyzed its influence on caspase-3 activation and vulnerability to ER stress. Cells expressing caspase-12 were more vulnerable to ER stress than cells expressing the empty vector, concomitant with increased activation of caspase-3. These findings suggested that activation of ER-resident caspase-12 indirectly activates cytoplasmic caspase-3 and might be important in ER stress-induced neuronal apoptosis.
authors.affiliation: Department of Anatomy and Neuroscience, Osaka University Medical School, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hitomi
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
authors.forename: Manabu
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Akiko
authors.initials: A
authors.lastname: Honda
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053454:Caspase 12; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism* / Q000502:physiology; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D014415:Tunicamycin; C506444:CASP12 protein, human; C505407:CASP3 protein, human; D053454:Caspase 12; D053148:Caspase 3; D020169:Caspases