Both Caspase-Dependent and Caspase-Independent Pathways May Be Involved in Hippocampal CA1 Neuronal Death Because of Loss of Cytochrome c from Mitochondria in a Rat Forebrain Ischemia Model
| Autor: | Hideyoshi Fujihara, Koki Shimoji, Chaoran Wu, Kiichiro Taga, Ren-Zhi Zhan, Makoto Naito, Sihua Qi |
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| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Blotting Western Ischemia Fluorescent Antibody Technique Apoptosis Cytochrome c Group Caspase 3 DNA Fragmentation Cycloheximide Hippocampal formation Hippocampus 030218 nuclear medicine & medical imaging 03 medical and health sciences chemistry.chemical_compound Prosencephalon 0302 clinical medicine Internal medicine In Situ Nick-End Labeling medicine Animals Vasospasm Intracranial Enzyme Inhibitors Rats Wistar Ischemic Preconditioning Neurons Protein Synthesis Inhibitors biology Cytochrome c Dentate gyrus medicine.disease Caspase Inhibitors Mitochondria Rats Endocrinology nervous system Neurology chemistry Caspases biology.protein Ischemic preconditioning Neurology (clinical) Cardiology and Cardiovascular Medicine Oligopeptides Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 21:529-540 |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1097/00004647-200105000-00007 |
| Popis: | In a rat forebrain ischemia model, the authors examined whether loss of cytochrome c from mitochondria correlates with ischemic hippocampal CA1 neuronal death and how cytochrome c release may shape neuronal death. Forebrain ischemia was induced by bilateral common carotid artery occlusion with simultaneous hypotension for 10 minutes. After reperfusion, an early rapid depletion of mitochondrial cytochrome c and a late phase of diffuse redistribution of cytochrome c occurred in the hippocampal CA1 region, but not in the dentate gyrus and CA3 regions. Intracerebroventricular administration of Z-DEVD-FMK, a relatively selective caspase-3 inhibitor, provided limited but significant protection against ischemic neuronal damage on day 7 after reperfusion. Treatment with 3 minutes of ischemia (ischemic preconditioning) 48 hours before the 10-minute ischemia attenuated both the early and late phases of cytochrome c redistribution. In another subset of animals treated with cycloheximide, a general protein synthesis inhibitor, the late phase of cytochrome c redistribution was inhibited, whereas most hippocampal CA1 neurons never regained mitochondrial cytochrome c. Examination of neuronal survival revealed that ischemic preconditioning prevents, whereas cycloheximide only delays, ischemic hippocampal CA1 neuronal death. DNA fragmentation detected by terminal deoxytransferase-mediated dUTP-nick end labeling (TUNEL) in situ was largely attenuated by ischemic preconditioning and moderately reduced by cycloheximide. These results indicate that the loss of cytochrome c from mitochondria correlates with hippocampal CA1 neuronal death after transient cerebral ischemia in relation to both caspase-dependent and -independent pathways. The amount of mitochondrial cytochrome c regained may determine whether ischemic hippocampal CA1 neurons survive or succumb to late-phase death. |
| Databáze: | OpenAIRE |
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