Nuclear translocation of apoptosis-inducing factor after focal cerebral ischemia

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Keyword

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

Publication and Content Type

ref (subject category)

art (subject category)