| Autor: | Graham Mouw, Warren R. Selman, Yifang Zhou, Robert A. Ratcheson, W. David Lust, Jennifer L. Zechel |
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| Rok vydání: | 2002 |
| Předmět: |
Programmed cell death
Pathology medicine.medical_specialty biology business.industry Cytochrome c Ischemia Infarction Pharmacology medicine.disease Biochemistry Neuroprotection Cellular and Molecular Neuroscience Apoptosis Enzyme inhibitor biology.protein medicine Neurology (clinical) business Caspase |
| Zdroj: | Metabolic Brain Disease. 17:143-151 |
| ISSN: | 0885-7490 |
| Popis: | Cerebral ischemia initiates a program of cell death known as apoptosis. Early steps in these death promoting events are the release of cytochrome c from the mitochondria and activation of caspase-9. The purpose of this report is to determine if the administration of a specific caspase-9 inhibitor, Z-Leu-Glu(Ome)-His-Asp(Ome)-FMK·TFA (Z-LEHD-FMK) would attenuate apoptosis and the resultant brain injury after ischemia. Adult Wistar rats underwent 3 h of temporary middle cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. An intraventricular injection of 4.8 μg of Z-LEHD-FMK was given 15-min postreperfusion. Administration of the caspase-9 inhibitor, Z-LEHD-FMK, to the experimental group (n = 12) reduced total infarction volume by 49% (p < 0.05) and improved neurological outcome by 63% (p < 0.01) as compared to the control group (n = 12). Western blot analysis of animals that underwent ischemia-reperfusion showed the appearance of the active form of caspase-9. Inhibition of caspase-9, the apical caspase in cytochrome-c-dependent apoptosis, is an effective intervention to attenuate neurological injury after focal ischemia. |
| Databáze: | OpenAIRE |
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