| First Author | Young C | Year | 2003 |
| Journal | Cell Death Differ | Volume | 10 |
| Issue | 10 | Pages | 1148-55 |
| PubMed ID | 14502238 | Mgi Jnum | J:115656 |
| Mgi Id | MGI:3692043 | Doi | 10.1038/sj.cdd.4401277 |
| Citation | Young C, et al. (2003) Ethanol-induced neuronal apoptosis in vivo requires BAX in the developing mouse brain. Cell Death Differ 10(10):1148-55 |
| abstractText | A single episode of ethanol intoxication triggers widespread apoptotic neurodegeneration in the infant rat or mouse brain. The cell death process occurs over a 6-16 h period following ethanol administration, is accompanied by a robust display of caspase-3 enzyme activation, and meets ultrastructural criteria for apoptosis. Two apoptotic pathways (intrinsic and extrinsic) have been described, either of which may culminate in the activation of caspase-3. The intrinsic pathway is regulated by Bax and Bcl-XL and involves Bax-induced mitochondrial dysfunction and release of cytochrome c as antecedent events leading to caspase-3 activation. Activation of caspase-8 is a key event preceding caspase-3 activation in the extrinsic pathway. In the present study, following ethanol administration to infant mice, we found no change in activated caspase-8, which suggests that the extrinsic pathway is not involved in ethanol-induced apoptosis. We also found that ethanol triggers robust caspase-3 activation and apoptotic neurodegeneration in C57BL/6 wildtype mice, but induces neither phenomenon in homozygous Bax-deficient mice. Therefore, it appears that ethanol-induced neuroapoptosis is an intrinsic pathway-mediated phenomenon involving Bax-induced disruption of mitochondrial membranes and cytochrome c release as early events leading to caspase-3 activation. |
