BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia
| Autor: | Dean A. Le, Sunu S. Thomas, Nikolaus Plesnila, Sepideh Amin-Hanjani, Stanley J. Korsmeyer, Sandra S. Zinkel, Michael A. Moskowitz, Jianhua Qiu, Daniel S. Kohane, Alberto Chiarugi, Yonqin Wu |
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| Rok vydání: | 2001 |
| Předmět: |
Programmed cell death
Ischemia Apoptosis Mice Transgenic Caspase 3 Mitochondrion Pharmacology Biology Caspase 8 Brain Ischemia Brain ischemia Mice medicine Animals Neurons Multidisciplinary Cytochrome c Biological Sciences medicine.disease Oxygen Glucose Phenotype Biochemistry biology.protein Carrier Proteins BH3 Interacting Domain Death Agonist Protein |
| Zdroj: | Proceedings of the National Academy of Sciences. 98:15318-15323 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.261323298 |
| Popis: | Mitochondria and cytochrome c release play a role in the death of neurons and glia after cerebral ischemia. In the present study, we investigated whether BID, a proapoptotic promoter of cytochrome c release and caspase 8 substrate, was expressed in brain, activated after an ischemic insult in vivo and in vitro , and contributed to ischemic cell death. We detected BID in the cytosol of mouse brain and primary cultured mouse neurons and demonstrated, by using recombinant caspase 8, that neuronal BID also is a caspase 8 substrate. After 2 h of oxygen/glucose deprivation, BID cleavage was detected in neurons concurrent with caspase 8 activation but before caspase 3 cleavage. Bid −/− neurons were resistant to death after oxygen/glucose deprivation, and caspase 3 cleavage was significantly reduced; however, caspase 8 cleavage did not differ from wild type. In vivo , BID was cleaved 4 h after transient middle cerebral artery occlusion. Infarct volumes and cytochrome c release also were less in Bid −/− mice (−67% and −41%, respectively) after mild focal ischemia. These findings suggest that BID and the mitochondrial-amplification pathway promoting caspase activation contributes importantly to neuronal cell death after ischemic insult. |
| Databáze: | OpenAIRE |
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