Translocation of apoptosis-inducing factor in cerebellar granule cells exposed to neurotoxic agents inducing oxidative stress.
We have previously shown that the neurotoxic compounds colchicine, methylmercury (MeHg) and hydrogen peroxide (H2O2) cause apoptosis in primary cultures of cerebellar granule cells (CGC), characterized by nuclear condensation and high-molecular weight DNA fragmentation. However, only colchicine triggers the activation of caspases, suggesting that factors other than caspase-activated DNase (CAD) are responsible for DNA cleavage in the other two models. Here we report that the two agents that cause oxidative stress, MeHg (1 micro m) and H2O2 (50 micro m), induce translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus in CGC. Our data suggest that, in absence of caspase activity, AIF translocation could be a key event leading to chromatin condensation and DNA degradation in CGC exposed to MeHg and H2O2.
Fonfría
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E
Institute of Environmental Medicine, Division of Toxicology and Neurotoxicology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Daré
E
E
Benelli
M
M
Suñol
C
C
Ceccatelli
S
S
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D018929:Cell Culture Techniques; D002467:Cell Nucleus / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053938:DNA Fragmentation; D005420:Flavoproteins / Q000187:drug effects / Q000378:metabolism*; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006861:Hydrogen Peroxide / Q000009:adverse effects; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000009:adverse effects; D008928:Mitochondria / Q000378:metabolism*; D016877:Oxidants / Q000009:adverse effects*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D008767:Methylmercury Compounds; D016877:Oxidants; D006861:Hydrogen Peroxide; C020771:methylmercury hydroxide