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 µm) and H2O2 (50 µm), 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.This work was supported by grants from the Swedish Research Council, the European Commission, and the Spanish Ministry of Health and Generalitat de Catalunya, Spain. E. F. is a recipient of a predoctoral fellowship from the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)