title: Role of caspases and mitochondria in the steroid-induced programmed cell death of a motoneuron during metamorphosis.
abstract: Accessory planta retractor (APR) motoneurons of the hawk moth, Manduca sexta, undergo a   segment-specific pattern of programmed cell death (PCD) 24 to 48 h after pupal ecdysis (PE). Cell culture   experiments show that the PCD of APRs in abdominal segment 6 [APR(6)s] is a cell-autonomous   response to the steroid hormone 20-hydroxyecdysone (20E) and involves mitochondrial demise and cell   shrinkage. Twenty-four hours before PE, at stage W3-noon, APR(6)s require further 20E exposure and   protein synthesis (as tested with cycloheximide) to undergo PCD, and death can be blocked by a   broad-spectrum caspase inhibitor. By PE, death is 20E- and protein synthesis-independent and the   caspase inhibitor blocks cell shrinkage but not loss of mitochondrial function. Thus, the commitment to   mitochondrial demise precedes the commitment to execution events. The phenotype of necrotic cell death   induced by a mitochondrial electron transfer inhibitor differs unambiguously from 20E-induced PCD. By   inducing PCD pharmacologically, the readiness of APR(6)s to execute PCD was found to increase during   the final larval instar. These data suggest that the 20E-induced PCD of APR(6)s includes a   premitochondrial phase which includes 20E-induced synthetic events and apical caspase activity, a   mitochondrial phase which culminates in loss of mitochondrial function, and a postmitochondrial phase   during which effector caspases are activated and APR(6) is destroyed.
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, Oregon,   97403-1254, USA.    
authors.forename: K L
authors.initials: KL
authors.lastname: Hoffman
authors.forename: J C
authors.initials: JC
authors.lastname: Weeks
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004441:Ecdysterone / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D007814:Larva; D018402:Manduca / Q000254:growth & development*; D008675:Metamorphosis, Biological; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D011679:Pupa; D013804:Thenoyltrifluoroacetone / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D015853:Cysteine Proteinase Inhibitors; D003609:Dactinomycin; D013804:Thenoyltrifluoroacetone; D004441:Ecdysterone; D003513:Cycloheximide; D020169:Caspases