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Nuclear translocation and calpain-dependent reduction of Bcl-2 after neonatal cerebral hypoxia-ischemia
- Source :
- Brain, behavior, and immunity. 24(5)
- Publication Year :
- 2009
-
Abstract
- Apoptosis-related mechanisms are important in the pathophysiology of hypoxic–ischemic injury in the neonatal brain. Caspases are the major executioners of apoptosis, but there are a number of upstream players that influence the cell death pathways. The Bcl-2 family proteins are important modulators of mitochondrial permeability, working either to promote or prevent apoptosis. In this study we focused on the anti-apoptotic Bcl-2 protein after neonatal cerebral hypoxia–ischemia (HI) in 8-day-old rats. Bcl-2 translocated to nuclei and accumulated there over the first 24 h of reperfusion after HI, as judged by immunohistochemistry and immuno-electron microscopy. We also found that the total level of Bcl-2 decreased after HI in vivo and after ionophore challenge in cultured human neuroblastoma (IMR-32) cells in vitro. Furthermore, the Bcl-2 reduction was calpain-dependent, because it could be prevented by the calpain inhibitor CX295 both in vivo and in vitro, suggesting cross-talk between excitotoxic and apoptotic mechanisms.
- Subjects :
- Male
Programmed cell death
Immunology
Blotting, Western
Active Transport, Cell Nucleus
Apoptosis
Behavioral Neuroscience
Bcl-2-associated X protein
In vivo
Cell Line, Tumor
medicine
Animals
Humans
Rats, Wistar
Microscopy, Immunoelectron
Caspase
Cells, Cultured
bcl-2-Associated X Protein
Cell Nucleus
Analysis of Variance
biology
Endocrine and Autonomic Systems
Calpain
Immunohistochemistry
In vitro
Cell biology
Rats
Cell nucleus
medicine.anatomical_structure
Animals, Newborn
Proto-Oncogene Proteins c-bcl-2
Hypoxia-Ischemia, Brain
biology.protein
Female
Subjects
Details
- ISSN :
- 10902139
- Volume :
- 24
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Brain, behavior, and immunity
- Accession number :
- edsair.doi.dedup.....5989e2e8fcb19b759034892c63fdc293