Artikel
Role of the Apoptosis Inducing Factor (AIF) for neuronal cell death following traumatic brain injury
Rolle von Apoptose induzierendem Faktor (AIF) für den neuronalen Zelltod nach Schädel-Hirn-Trauma
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Autoren
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A. Ardeshiri
- Neurochirurgische Klinik, Klinikum der Universität München - Großhadern
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A. Ardeshiri
- Neurochirurgische Klinik, Klinikum der Universität München - Großhadern
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E. J. Slemmer
- Erasmus MC, University of Rotterdam, Niederlande
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C. Culmsee
- Institut für Pharmazeutische Biologie, LMU München
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J. T. Weber
- Erasmus MC, University of Rotterdam, Niederlande
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N. Plesnila
- Neurochirurgische Klinik, Klinikum der Universität München - Großhadern
| Veröffentlicht: | 11. April 2007 |
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Gliederung
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Objective: Apoptosis inducing factor (AIF), a caspase-independent cell death protein, translocates from mitochondria to the nucleus in injured cells after traumatic brain injury. Results from in vivo studies suggest that this phenomenon occurs in neurons. In order to further investigate the role of AIF in neurons and astrocytes we investigated the influence of AIF expression on cell death in an in vitro trauma model.
Methods: Primary cultured mouse neurons and glial cells were subjected to trauma by membrane stretch injury. Mild (5.5 mm membrane stretch) or moderate (6.5 mm) trauma was applied. Cells were treated with AIF-siRNA and mutant-siRNA (control) in order to downregulate physiological AIF protein levels as demonstrated by PCR and Western blot analysis. Neurons and astrocytes were identified by MAP-2 and GFAP immunofluorescence, respectively. AIF translocation from mitochondria to the nucleus was shown by immunocytochemistry for AIF and DAPI nuclear staining.
Results: Immunofluorescence showed that translocation of AIF occurred only in neurons and not in glial cells. Both, AIF mRNA and AIF protein were downregulated by AIF-siRNA (-80%). The number of cells showing membrane damage was significantly decreased by AIF-siRNA (-26% for mild and -56% for moderate trauma) and the number of surviving neurons was significantly increased (p<0.001).
Conclusions: The present study proves that translocation of AIF 1) occurs only in neurons and not in astrocytes and 2) leads to neuronal cell death after traumatic cell injury. Therefore inhibition of AIF by AIF-siRNA or other means may be a therapeutic option for the treatment of secondary neuronal cell death following traumatic brain injury.
