Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia
AUTOR(ES)
Krajewski, Stanislaw
FONTE
The National Academy of Sciences
RESUMO
Caspase-9 is critical for cytochrome c (cyto-c)-dependent apoptosis and normal brain development. We determined that this apical protease in the cyto-c pathway for apoptosis resides inside mitochondria in several types of cells, including cardiomyocytes and many neurons. Caspase-9 is released from isolated mitochondria on treatment with Ca2+ or Bax, stimuli implicated in ischemic neuronal cell death that are known to induce cyto-c release from mitochondria. In neuronal cell culture models, apoptosis-inducing agents trigger translocation of caspase-9 from mitochondria to the nucleus, which is inhibitable by Bcl-2. Similarly, in an animal model of transient global cerebral ischemia, caspase-9 release from mitochondria and accumulation in nuclei was observed in hippocampal and other vulnerable neurons exhibiting early postischemic changes preceding apoptosis. Loss of mitochondrial barrier function during neuronal damage from ischemia or other insults therefore may play an important role in making certain caspases available to participate in apoptosis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21932Documentos Relacionados
- Oncogene-dependent apoptosis is mediated by caspase-9
- Evolutionary conservation of apoptosis mechanisms: Lepidopteran and baculoviral inhibitor of apoptosis proteins are inhibitors of mammalian caspase-9
- Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress
- Caspase-9 and APAF-1 form an active holoenzyme
- Analysis of Caspase-9 protein and microRNAs miR-21, miR-126 and miR-155 related to the apoptosis mechanism in the cerebellum of rats submitted to focal cerebral ischemia associated with an alcoholism model