1. Induction of necrotic cell death and mitochondrial permeabilization by heme binding protein 2/SOUL
- Author
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Zita Bognar, Andras Szigeti, Arpad Boronkai, Eniko Hocsak, Gabor Varbiro, Ferenc Gallyas, Orsolya Minik, Balazs Sumegi, Szabolcs Bellyei, and Balázs Gasz
- Subjects
Cell death ,Hemeproteins ,Programmed cell death ,Necrosis ,SOUL ,Heme binding protein 1 ,Biophysics ,Biology ,Pregnancy Proteins ,Biochemistry ,Permeability ,Flow cytometry ,Heme-Binding Proteins ,Mice ,Structural Biology ,Genetics ,medicine ,Animals ,Humans ,cardiovascular diseases ,Molecular Biology ,Calcimycin ,Etoposide ,chemistry.chemical_classification ,Mitochondrial permeability transition ,Reactive oxygen species ,medicine.diagnostic_test ,Ionophores ,Cytochrome c ,Cell Biology ,Molecular biology ,Antineoplastic Agents, Phytogenic ,Recombinant Proteins ,Mitochondria ,Glutathione S-transferase ,chemistry ,Mitochondrial permeability transition pore ,Mitochondrial Membranes ,biology.protein ,Cyclosporine ,NIH 3T3 Cells ,Calcium ,medicine.symptom ,Heme binding protein ,Carrier Proteins ,Immunosuppressive Agents - Abstract
We found that heme-binding protein 2/SOUL sensitised NIH3T3 cells to cell death induced by A23187 and etoposide, but it did not affect reactive oxygen species formation. In the presence of sub-threshold calcium, recombinant SOUL provoked mitochondrial permeability transition (mPT) in vitro that was inhibited by cyclosporine A (CsA). This effect was verified in vivo by monitoring the dissipation of mitochondrial membrane potential. Flow cytometry analysis showed that SOUL promoted necrotic death in A23187 and etoposide treated cells, which effect was prevented by CsA. These data suggest that besides its heme-binding properties SOUL promotes necrotic cell death by inducing mPT.
- Published
- 2006