Nuclear translocation of apoptosis-inducing factor after focal cerebral ischemia.

Abstract

Signaling cascades associated with apoptosis contribute to cell death after focal cerebral ischemia. Cytochrome c release from mitochondria and the subsequent activation of caspases 9 and 3 are critical steps. Recently, a novel mitochondrial protein, apoptosis-inducing factor (AIF), has been implicated in caspase-independent programmed cell death following its translocation to the nucleus. We, therefore, addressed the question whether AIF also plays a role in cell death after focal cerebral ischemia. We detected AIF relocation from mitochondria to nucleus in primary cultured rat neurons 4 and 8 hours after 4 hours of oxygen/glucose deprivation. In ischemic mouse brain, AIF was detected within the nucleus 1 hour after reperfusion after 45 minutes occlusion of the middle cerebral artery. AIF translocation preceded cell death, occurred before or at the time when cytochrome c was released from mitochondria, and was evident within cells showing apoptosis-related DNA fragmentation. From these findings, we infer that AIF may be involved in neuronal cell death after focal cerebral ischemia and that caspase-independent signaling pathways downstream of mitochondria may play a role in apoptotic-like cell death after experimental stroke.

• Authors: Nikolaus Plesnila, Changlian Zhu, Carsten Culmsee, Moritz Gröger, Michael A Moskowitz, Klas Blomgren
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 24 Issue 4 Pg. 458-66 (Apr 2004) ISSN: 0271-678X [Print] United States
• PMID: 15087715 (Publication Type: Journal Article)

Chemical References

• Aifm1 protein, rat
• Apoptosis Inducing Factor
• Culture Media
• Flavoproteins
• Membrane Proteins
• Pdcd8 protein, mouse
• Glucose
• Oxygen

Topics

• Animals
• Apoptosis
• Apoptosis Inducing Factor
• Blotting, Western
• Cell Count
• Cell Nucleus (metabolism)
• Cells, Cultured
• Cerebral Cortex (cytology, metabolism)
• Culture Media
• Disease Models, Animal
• Flavoproteins (metabolism)
• Glucose (metabolism)
• Hippocampus (cytology, metabolism)
• Immunohistochemistry
• Ischemic Attack, Transient (metabolism)
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Mitochondria (metabolism)
• Neurons (cytology, metabolism)
• Oxygen (metabolism)
• Rats
• Rats, Sprague-Dawley