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Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia
Open accessAbstract
Caspase-9 is critical for cytochrome c (cyto-c)-dependent apoptosis and normal brain development. We determined that this apical protease in the cyto-c pathway for apoptosis resides inside mitochondria in several types of cells, including cardiomyocytes and many neurons. Caspase-9 is released from isolated mitochondria on treatment with Ca 2+ or Bax, stimuli implicated in ischemic neuronal cell death that are known to induce cyto-c release from mitochondria. In neuronal cell culture models, apoptosis-inducing agents trigger translocation of caspase-9 from mitochondria to the nucleus, which is inhibitable by Bcl-2. Similarly, in an animal model of transient global cerebral ischemia, caspase-9 release from mitochondria and accumulation in nuclei was observed in hippocampal and other vulnerable neurons exhibiting early postischemic changes preceding apoptosis. Loss of mitochondrial barrier function during neuronal damage from ischemia or other insults therefore may play an important role in making certain caspases available to participate in apoptosis.
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Citations
Cited by
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598
Mitochondrial control of cell death
Kroemer, G., & Reed, J. C. (2000) · Nature Medicine · doi:10.1038/74994 · Cited by 3,103
Self-citationBrain ischemia and reperfusion: molecular mechanisms of neuronal injury
White, B. C., Sullivan, J. M., DeGracia, D. J., O’Neil, B. J., Neumar, R. W., Grossman, L. I., Rafols, J. A., & Krause, G. S. (2000) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(00)00386-5 · Cited by 796
Vascular endothelial growth factor: Direct neuroprotective effect in in vitro ischemia
Jin, K. L., Mao, X. O., & Greenberg, D. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.18.10242 · Cited by 684
Madesh, M., & Hajnóczky, G. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200105057 · Cited by 538
Metadata
- Authors
- Krajewski, S., Krajewska, M., Ellerby, L. M., Welsh, K., Xie, Z., Deveraux, Q. L., Salvesen, G. S., Bredesen, D. E., Rosenthal, R. E., Fiskum, G., & Reed, J. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-05-11
- Volume
- 96
- Issue
- 10
- Pages
- 5752-5757
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2026761074
- Cited by
- 542
- References
- 0
- FWCI
- 25.01
- Type
- journal article
- Language
- en
- Open access
- green
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- Krajewski, S., Krajewska, M., Ellerby, L. M., Welsh, K., Xie, Z., Deveraux, Q. L., Salvesen, G. S., Bredesen, D. E., Rosenthal, R. E., Fiskum, G., & Reed, J. C. (1999). Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.10.5752
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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