Nuclear Translocation and Calpain-Dependent Reduction of Bcl-2 After Neonatal Cerebral Hypoxia–Ischemia

UNCP Author/Contributor (non-UNCP co-authors, if there are any, appear on document)
Dr . Ben Bahr, William C. Friday Chair and Professor of Molecular Biology and Biochemistry (Creator)
The University of North Carolina at Pembroke (UNCP )
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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.

Additional Information

Brain, Behavior, and Immunity
Language: English
Date: 2009
Apoptosis, Neonatal Cerebral Hypoxia–Ischemia, Bcl-2 Family Proteins, Caspases, Neuronal Death, Immuno-Electron Microscopy, Neonatal Brain

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