Induction of necrotic cell death and mitochondrial permeabilization by heme binding protein 2/SOUL.
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.
Szigeti
Andras
A
Institute of Oncotherapy, University of Pécs, Pécs, Hungary.
Bellyei
Szabolcs
S
Gasz
Balazs
B
Boronkai
Arpad
A
Hocsak
Eniko
E
Minik
Orsolya
O
Bognar
Zita
Z
Varbiro
Gabor
G
Sumegi
Balazs
B
Gallyas
Ferenc
F
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
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