Caspase-3 Cleavage and Nuclear Localization of Caspase-Activated DNase in Human Temporal Lobe Epilepsy
| Autor: | Clara K. Schindler, David C. Henshall, Jochen H. M. Prehn, Roger P. Simon, Erik G. Pearson, Norman K. So, Helena P. Bonner |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Programmed cell death
Pathology medicine.medical_specialty Apoptosis Caspase 3 Cell Fractionation Hippocampus behavioral disciplines and activities Caspase-activated DNase medicine Humans Caspase Cell Nucleus Deoxyribonucleases Endodeoxyribonucleases biology Apoptosis Inducing Factor Subcellular localization Molecular biology nervous system diseases Epilepsy Temporal Lobe nervous system Neurology Caspases biology.protein DNA fragmentation Neurology (clinical) Cardiology and Cardiovascular Medicine Deoxyribonuclease I psychological phenomena and processes Signal Transduction |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 26:583-589 |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1038/sj.jcbfm.9600219 |
| Popis: | Programmed cell death (apoptosis) signaling pathways have been implicated in seizure-induced neuronal death and the pathogenesis of human temporal lobe epilepsy (TLE). End-stage DNA fragmentation during cell death may be mediated by nucleases including caspase-activated DNase (CAD), apoptosis-inducing factor (AIF) and endonuclease G. In the present study, we investigated the subcellular localization of these nucleases in resected hippocampus from TLE patients and autopsy controls. Subcellular fractionation determined levels of CAD were significantly higher in the nuclear fraction of TLE samples compared with controls, and semiquantitative immunohistochemistry revealed cleaved caspase-3 positive cells in TLE sections but not controls. While mitochondrial levels of AIF and endonuclease G were higher in TLE samples than controls, nuclear localization of AIF was limited and restricted to cells that were negative for cleaved caspase-3. Nuclear accumulation of endonuclease G was not found in TLE samples. These data support ongoing caspase-dependent apoptosis signaling in human TLE and suggest that interventions targeting such pathways may have potential as adjunctive neuroprotective therapy in epilepsy. |
| Databáze: | OpenAIRE |
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