Fas/CD95/APO-1 can function as a death receptor for neuronal cells in vitro and in vivo and is upregulated following cerebral hypoxic-ischemic injury to the developing rat brain
| Autor: | A. David Edwards, Umesh Joashi, B. Huseyin Mehmet, Dietger Stibenz, Kirsty Greenwood, Ursula Felderhoff-Mueser, Mary Kozma, Deanna L. Taylor |
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| Rok vydání: | 2000 |
| Předmět: |
Pathology
medicine.medical_specialty Hippocampus Apoptosis Caspase 8 PC12 Cells Pathology and Forensic Medicine Downregulation and upregulation In vivo medicine Animals fas Receptor Rats Wistar Receptor Caspase Cerebral Cortex Neurons biology General Neuroscience Brain Fas receptor Cell biology Rats Up-Regulation nervous system Animals Newborn Immunoglobulin M Caspases Hypoxia-Ischemia Brain biology.protein Neurology (clinical) Research Article |
| Zdroj: | Brain Pathol |
| ISSN: | 1015-6305 |
| Popis: | Fas/CD95/Apo-1 is a cell surface receptor that transduces apoptotic death signals following activation and has been implicated in triggering apoptosis in infected or damaged cells in disease states. Apoptosis is a major mechanism of neuronal loss following hypoxic-ischemic injury to the developing brain, although the role of Fas in this process has not been studied in detail. In the present study, we have investigated the expression and function of Fas in neuronal cells in vitro and in vivo. Fas was found to be expressed in the 14 day old rat brain, with strongest expression in the cortex, hippocampus and cerebellum. Cross-linking of Fas induced neuronal apoptosis both in neuronal PC12 cells in culture and following intracerebral injection in vivo, indicating that neuronal Fas was functional as a death receptor. This death was shown to be caspase dependent in primary neuronal cultures and was blocked by the selective caspase 8 inhibitor IETD. Finally, cerebral hypoxia-ischemia resulted in a strong lateralised upregulation of Fas in the hippocampus, that peaked six to twelve hours after the insult and was greater on the side of injury. These results suggest that Fas may be involved in neuronal apoptosis following hypoxic-ischemic injury to the developing brain. |
| Databáze: | OpenAIRE |
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