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Bcl-2 transfection via herpes simplex virus blocks apoptosis-inducing factor translocation after focal ischemia in the rat.
- Source :
-
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2004 Jun; Vol. 24 (6), pp. 681-92. - Publication Year :
- 2004
-
Abstract
- Apoptosis plays a critical role in many neurologic diseases, including stroke. Cytochrome c release and activation of various caspases are known to occur after focal and global ischemia. However, recent reports indicate that caspase-independent pathways may also be involved in ischemic damage. Apoptosis-inducing factor (AIF) is a novel flavoprotein that helps mediate caspase-independent apoptotic cell death. AIF translocates from mitochondria to nuclei where it induces caspase-independent DNA fragmentation. Bcl-2, a mitochondrial membrane protein, protects against apoptotic and necrotic death induced by different insults, including cerebral ischemia. In the present study, Western blots confirmed that AIF was normally confined to mitochondria but translocated to nuclei or cytosol 8, 24, and 48 hours after onset of ischemia. Overall, AIF protein levels also increased after stroke. Confocal microscopy further demonstrated that nuclear AIF translocation occurred in the peri-infarct region but not in the ischemic core where only some cytosolic AIF release was observed. Our data also suggest that AIF translocated into nuclei after cytochrome c was released into the cytosol. Bcl-2 transfection in the peri-infarct region blocked nuclear AIF translocation and improved cortical neuron survival.
- Subjects :
- Animals
Apoptosis
Apoptosis Inducing Factor
Brain Ischemia pathology
Cell Nucleus metabolism
Cytochromes c metabolism
Fluorescent Dyes
Humans
Mitochondria metabolism
Neurons cytology
Neurons metabolism
Protein Transport physiology
Proto-Oncogene Proteins c-bcl-2 genetics
Rats
Rats, Sprague-Dawley
Simplexvirus genetics
Subcellular Fractions chemistry
Brain Ischemia metabolism
Flavoproteins metabolism
Membrane Proteins metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
Simplexvirus metabolism
Transfection
Subjects
Details
- Language :
- English
- ISSN :
- 0271-678X
- Volume :
- 24
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 15181376
- Full Text :
- https://doi.org/10.1097/01.WCB.0000127161.89708.A5