title: Induction of necrotic cell death and mitochondrial permeabilization by heme binding protein 2/SOUL.
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.
authors.affiliation: Institute of Oncotherapy, University of Pécs, Pécs, Hungary.
authors.forename: Andras
authors.initials: A
authors.lastname: Szigeti
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Bellyei
authors.forename: Balazs
authors.initials: B
authors.lastname: Gasz
authors.forename: Arpad
authors.initials: A
authors.lastname: Boronkai
authors.forename: Eniko
authors.initials: E
authors.lastname: Hocsak
authors.forename: Orsolya
authors.initials: O
authors.lastname: Minik
authors.forename: Zita
authors.initials: Z
authors.lastname: Bognar
authors.forename: Gabor
authors.initials: G
authors.lastname: Varbiro
authors.forename: Balazs
authors.initials: B
authors.lastname: Sumegi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Gallyas
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009336:Necrosis / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; C516258:HEBP2 protein, human; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D007166:Immunosuppressive Agents; D007476:Ionophores; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; D000001:Calcimycin; D005047:Etoposide; D016572:Cyclosporine; D002118:Calcium