title: BMAP-28, an antibiotic peptide of innate immunity, induces cell death through opening of the mitochondrial permeability transition pore.
abstract: 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.
authors.affiliation: Department of Biotechnology and Biomedical Sciences, University of Udine, via Cotonificio 108, I-33100 Udine, Italy. angela.risso@dbea.uniud.it
authors.forename: Angela
authors.initials: A
authors.lastname: Risso
authors.forename: Enrico
authors.initials: E
authors.lastname: Braidot
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Sordano
authors.forename: Angelo
authors.initials: A
authors.lastname: Vianello
authors.forename: Francesco
authors.initials: F
authors.lastname: Macrì
authors.forename: Barbara
authors.initials: B
authors.lastname: Skerlavaj
authors.forename: Margherita
authors.initials: M
authors.lastname: Zanetti
authors.forename: Renato
authors.initials: R
authors.lastname: Gennaro
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernardi
mesh_terms: 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
chemical_list: 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