Aim: 

Isoferritins purified from rat hepatocyte conditioned media (CM) significantly stimulate apoptosis in primary rat hepatocytes, involving p53, the Fas pathway and the proapoptotic mitochondrial pathways. Since iron ions may be liberated from ferritin thus triggering apoptosis via the Fenton reaction followed by lipid peroxidation, this potential scenario was investigated.

Methods: 

Both the distribution of ferritin and HNE-modified proteins was analyzed immunohistochemically in primary rat hepatocyte cultures after treatment with purified isoferritins. Furthermore, the potential inhibition of apoptosis by the antioxidant trolox and the iron chelator desferrioxamine was investigated.

Results: 

Both ferritin and HNE-modified proteins were found to be localized close to the nuclear envelope indicating that a) ferritin may protect the vital genome by sequestering free ferrous iron and b) may initiate the release of iron and therefore Fenton-reaction mediated nuclear damage in isoferritin responsive cells. The latter assumption is supported by the observation that trolox inhibits isoferritin stimulated apoptosis. Furthermore, iron chelation by desferrioxamine reduces the incidence of apoptosis to nearly control level.

Conclusion: 

Cell isolation and primary culture pose a more or less heavy stress to the cells both enzymatically, mechanically and oxidative. Therefore, ferritin can be considered to act as a stress response protein with the function to remove potentially harmful stressed cells and thus supports tissue regeneration/restoration. This assumption is supported by the fact, that all pathological developments originating from or being accompanied by inflammatory processes also show elevated levels of ferritin (supported by COST B35).