Differential Expression of Apoptotic Protease-Activating Factor-1 and Caspase-3 Genes and Susceptibility to Apoptosis during Brain Development and after Traumatic Brain Injury
| Autor: | Koichiro Yoshihara, Alan I. Faden, Geping Wang, Katsuya Ota, Alexander G. Yakovlev, Vilen A. Movsesyan, Wei-Li Bao |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Aging Cell Survival Traumatic brain injury Blotting Western Apoptosis Cytochrome c Group Caspase 3 Biology Wounds Nonpenetrating Rats Sprague-Dawley Cytosol Deoxyadenine Nucleotides Downregulation and upregulation Gene expression medicine Animals APAF1 ARTICLE Psychological repression Cells Cultured Cerebral Cortex Messenger RNA Cell-Free System General Neuroscience Brain Gene Expression Regulation Developmental Proteins medicine.disease Rats Cell biology Enzyme Activation Disease Models Animal Apoptotic Protease-Activating Factor 1 Brain Injuries Caspases Protein Biosynthesis Signal Transduction |
| Zdroj: | The Journal of Neuroscience. 21:7439-7446 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.21-19-07439.2001 |
| Popis: | Neuronal apoptosis plays an essential role in early brain development and contributes to secondary neuronal loss after acute brain injury. Recent studies have provided evidence that neuronal susceptibility to apoptosis induced by traumatic or ischemic injury decreases during brain development. However, the molecular mechanisms responsible for this age-dependent phenomenon remain unclear. Here we demonstrate that, during brain maturation, the potential of the intrinsic apoptotic pathway is progressively reduced and that such repression is associated with downregulation of apoptotic protease-activating factor-1 (Apaf-1) and caspase-3 gene expression. A similar decline in apoptotic susceptibility associated with downregulation of Apaf-1 expression as a function of developmental age was also found in cultured primary rat cortical neurons. Injury-induced cytochrome c-specific cleavage of caspase-9 followed by activation of caspase-3 in mature brain correlated with marked increases in Apaf-1 and caspase-3 mRNA and protein expression. These results suggest that differential expression of Apaf-1 and caspase-3 genes may underlie regulation of apoptotic susceptibility during brain development, as well as after acute injury to mature brain, through the intrinsic pathway of caspase activation. |
| Databáze: | OpenAIRE |
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