BMAP-28, an antibiotic peptide of innate immunity, induces cell death through opening of the mitochondrial permeability transition pore.
BMAP-28, a bovine antimicrobial peptide of the cathelicidin family, induces membrane permeabilization and death in human tumor cell lines and in activated, but not resting, human lymphocytes. In addition, we found that BMAP-28 causes depolarization of the inner mitochondrial membrane in single cells and in isolated mitochondria. The effect of the peptide was synergistic with that of Ca(2+) and inhibited by cyclosporine, suggesting that depolarization depends on opening of the mitochondrial permeability transition pore. The occurrence of a permeability transition was investigated on the basis of mitochondrial permeabilization to calcein and cytochrome c release. We show that BMAP-28 permeabilizes mitochondria to entrapped calcein in a cyclosporine-sensitive manner and that it releases cytochrome c in situ. Our results demonstrate that BMAP-28 is an inducer of the mitochondrial permeability transition pore and that its cytotoxic potential depends on its effects on mitochondrial permeability.
Risso
Angela
A
Department of Biotechnology and Biomedical Sciences, University of Udine, via Cotonificio 108, I-33100 Udine, Italy. angela.risso@dbea.uniud.it
Braidot
Enrico
E
Sordano
Maria Concetta
MC
Vianello
Angelo
A
Macrì
Francesco
F
Skerlavaj
Barbara
B
Zanetti
Margherita
M
Gennaro
Renato
R
Bernardi
Paolo
P
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D007473:Ion Channels; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011506:Proteins / Q000494:pharmacology*; D020298:U937 Cells
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C102360:BMAP-28; D003574:Cytochrome c Group; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007473:Ion Channels; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011506:Proteins; D016572:Cyclosporine; D002118:Calcium; C007740:fluorexon