p53, a tumour suppressor, is involved in DNA repair and cell death processes and mediates apoptosis in response to death stimuli by transcriptional activation of pro-apoptotic genes and by transcription-independent mechanisms. In the latter process, p53 induces permeabilization of the outer mitochondrial membrane by forming an inhibitory complex with a protective Bcl-2 family protein, resulting in cytochrome c release in several cell line systems. However, it is unclear how the mitochondrial p53 pathway mediates neuronal apoptosis after cerebral ischaemia. We examined interaction between the mitochondrial p53 pathway and vulnerable hippocampal CA1 neurons using a tGCI (transient global cerebral ischaemia) rat model. We showed mitochondrial translocation of p53 and its binding to Bcl-XL. Mitochondrial p53 translocation, interaction between p53 and Bcl-XL, and cytochrome c release from mitochondria and subsequent CA1 neuronal death were prevented by pifithrin-α, a p53-specific inhibitor. These results suggest that the mitochondrial p53 pathway plays a role in delayed CA1 neuronal death after tGCI.
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Conference Article|
October 25 2006
Mitochondrial translocation of p53 underlies the selective death of hippocampal CA1 neurons after global cerebral ischaemia
H. Endo;
H. Endo
1Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, 1201 Welch Road, MSLS #P314, Stanford, CA 94305-5487, U.S.A.
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A. Saito;
A. Saito
1Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, 1201 Welch Road, MSLS #P314, Stanford, CA 94305-5487, U.S.A.
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P.H. Chan
P.H. Chan
1
1Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, 1201 Welch Road, MSLS #P314, Stanford, CA 94305-5487, U.S.A.
1To whom correspondence should be addressed (email phchan@stanford.edu).
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Publisher: Portland Press Ltd
Received:
July 19 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (6): 1283–1286.
Article history
Received:
July 19 2006
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A correction has been published:
Mitochondrial translocation of p53 underlies the selective death of hippocampal CA1 neurons after global cerebral ischaemia
Citation
H. Endo, A. Saito, P.H. Chan; Mitochondrial translocation of p53 underlies the selective death of hippocampal CA1 neurons after global cerebral ischaemia. Biochem Soc Trans 1 December 2006; 34 (6): 1283–1286. doi: https://doi.org/10.1042/BST0341283
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