title: Activation of caspase-12, an endoplasmic reticulum resident caspase, after permanent focal ischemia in rat.
abstract: The endoplasmic reticulum (ER) is emerging as a contributory component of cell death after ischemia. Since caspase-12 has been localized to the ER and is a novel signal for apoptosis, we examined the message levels and protein expression of caspase-12 after cerebral ischemia in vivo. Animals underwent permanent middle cerebral artery occlusion (MCAO) and were sacrificed 24 h after ischemia. Protein analysis revealed a significant increase in caspase-12 and a corresponding up-regulation of caspase-12 mRNA in the ischemia group compared with that in the sham group. Immunohistochemical analysis revealed diffuse positive immunostaining of caspase-12 throughout the striatum and cerebral cortex in animals that underwent ischemia, with more intense caspase-12 immunostaining in the striatum than in the cortex after ischemia. These results demonstrate that cerebral ischemia initiates an ER-based stress response that results in the transcriptional up-regulation and corresponding increased expression of caspase-12 protein, and may provide a new area for therapeutic intervention to ameliorate outcomes following stroke.
authors.affiliation: Department of Neurological Surgery, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4939, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Mouw
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Zechel
authors.forename: Jorge
authors.initials: J
authors.lastname: Gamboa
authors.forename: W David
authors.initials: WD
authors.lastname: Lust
authors.forename: Warren R
authors.initials: WR
authors.lastname: Selman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Ratcheson
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology*; D053454:Caspase 12; D020169:Caspases / Q000032:analysis / Q000096:biosynthesis*; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: C506443:Casp12 protein, rat; D053454:Caspase 12; D020169:Caspases