BACKGROUND AND PURPOSE: Reactive oxygen species produced during reperfusion may play a detrimental role in focal cerebral ischemia (FCI). We examined the protein expression of caspase-8, which plays a major role in both Fas-dependent and cytochrome c-dependent apoptotic pathways after FCI with or without reperfusion. Caspase-8 expression after transient FCI was compared between wild-type and transgenic mice that overexpress the cytosolic antioxidant copper/zinc superoxide dismutase (SOD1). METHODS: Adult male CD-1 mice were subjected to 1 hour of FCI and reperfusion or to permanent FCI by intraluminal blockade of the middle cerebral artery. DNA fragmentation was evaluated by genomic DNA gel electrophoresis. Caspase-8 expression was analyzed by Western blot. RESULTS: Caspase-8 was significantly induced 4 hours after transient FCI and remained at an increased level until 24 hours, whereas it was not modified after permanent FCI. Genomic DNA gel electrophoresis showed DNA laddering in a pattern similar to that seen in apoptosis, with a small amount of background smear 24 hours after transient FCI, whereas 25 hours of permanent FCI resulted in less DNA laddering with a strong background smear. Caspase-8 induction was significantly reduced in SOD1 transgenic mice compared with wild-type mice 4 hours after transient FCI. CONCLUSIONS: The results suggest that increased reactive oxygen species production during reperfusion may contribute to the induction of caspase-8, thereby exacerbating apoptosis after FCI.
BACKGROUND AND PURPOSE:Reactive oxygen species produced during reperfusion may play a detrimental role in focal cerebral ischemia (FCI). We examined the protein expression of caspase-8, which plays a major role in both Fas-dependent and cytochrome c-dependent apoptotic pathways after FCI with or without reperfusion. Caspase-8 expression after transient FCI was compared between wild-type and transgenic mice that overexpress the cytosolic antioxidant copper/zinc superoxide dismutase (SOD1). METHODS: Adult male CD-1mice were subjected to 1 hour of FCI and reperfusion or to permanent FCI by intraluminal blockade of the middle cerebral artery. DNA fragmentation was evaluated by genomic DNA gel electrophoresis. Caspase-8 expression was analyzed by Western blot. RESULTS:Caspase-8 was significantly induced 4 hours after transient FCI and remained at an increased level until 24 hours, whereas it was not modified after permanent FCI. Genomic DNA gel electrophoresis showed DNA laddering in a pattern similar to that seen in apoptosis, with a small amount of background smear 24 hours after transient FCI, whereas 25 hours of permanent FCI resulted in less DNA laddering with a strong background smear. Caspase-8 induction was significantly reduced in SOD1transgenic mice compared with wild-type mice 4 hours after transient FCI. CONCLUSIONS: The results suggest that increased reactive oxygen species production during reperfusion may contribute to the induction of caspase-8, thereby exacerbating apoptosis after FCI.
Authors: Marija Renic; Suresh N Kumar; Debebe Gebremedhin; Matthew A Florence; Nashaat Z Gerges; John R Falck; David R Harder; Richard J Roman Journal: Am J Physiol Heart Circ Physiol Date: 2012-01-13 Impact factor: 4.733
Authors: Aigang Lu; Joseph F Clark; Joseph P Broderick; Gail J Pyne-Geithman; Kenneth R Wagner; Pooja Khatri; Thomas Tomsick; Frank R Sharp Journal: Exp Neurol Date: 2009-01-07 Impact factor: 5.330
Authors: Ana V C Dutra; Hsiu-Fen Lin; Suh-Hang H Juo; Harvey Mohrenweiser; Souvik Sen; Raji P Grewal Journal: BMC Med Genet Date: 2006-11-06 Impact factor: 2.103
Authors: Leema Reddy Peddareddygari; Ana Virginia Dutra; Mark A Levenstien; Souvik Sen; Raji P Grewal Journal: BMC Neurol Date: 2009-07-22 Impact factor: 2.474