title: Comparison of Cytotoxic Activity in Leukemic Lineages Reveals Important Features of β-Hairpin Antimicrobial Peptides.
abstract: Several reports described different modes of cell death triggered by antimicrobial peptides (AMPs) due to direct effects on membrane disruption, and more recently by apoptosis and necrosis-like patterns. Cytotoxic curves of four β-hairpin AMPs (gomesin, protegrin, tachyplesin, and polyphemusin) were obtained from several human leukemic lineages and normal monocytes and Two cell lines were then selected based on their cytotoxic sensitivity. One was sensitive to AMPs (K562) and the other resistant (KG-1) and their effect compared between these lineages. Thus, these lineages were chosen to further investigate biological features related with their cytotoxicities to AMPs. Stimulation with AMPs produced cell death, with activation of caspase-3, in K562 lineage. Increase on the fluidity of plasmatic membrane by reducing cholesterol potentiated cytotoxicity of AMPs in both lineages. Quantification of internal and external gomesin binding to the cellular membrane of both K562 and KG-1 cells showed that more peptide is accumulated inside of K562 cells. Additionally, evaluation of multi-drug resistant pumps activity showed that KG-1 has more activity than K562 lineage. A comparison of intrinsic gene patterns showed great differences between K562 and KG-1, but stimulation with gomesin promoted few changes in gene expression patterns. Differences in internalization process through the plasma membrane, multidrug resistance pumps activity, and gene expression pattern are important features to AMPs regulated cell death. J. Cell. Biochem. 118: 1764-1773, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, R. Três de Maio 100, São Paulo 04044-020, SP, Brazil.
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Buri
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, R. Três de Maio 100, São Paulo 04044-020, SP, Brazil.
authors.forename: Heron F Vieira
authors.initials: HFV
authors.lastname: Torquato
authors.affiliation: Departamento de Nutrição, Universidade Federal de Pelotas, R. Gomes Carneiro, n°1, 96010-610, Pelotas, RS, Brazil.
authors.forename: Carlos Castilho
authors.initials: CC
authors.lastname: Barros
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven 06519, Connecticut.
authors.forename: Jaime S
authors.initials: JS
authors.lastname: Ide
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo, R. Três de Maio 100, São Paulo 04044-020, SP, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, R. Três de Maio 100, São Paulo 04044-020, SP, Brazil.|Centro Interdisciplinar de Investigação Bioquı́mica, Universidade de Mogi das Cruzes, Av. Dr. Cândido Xavier de Almeida Souza, 200. Mogi das Cruzes, SP, Brazil.
authors.forename: Edgar J
authors.initials: EJ
authors.lastname: Paredes-Gamero
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D010456:Peptides, Cyclic / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D010456:Peptides, Cyclic; C415987:gomesin; C057636:tachyplesin peptide, Tachypleus tridentatus; C062386:polyphemusin II; D053148:Caspase 3
keywords: ANTIMICROBIAL PEPTIDE; CELL DEATH; GENE EXPRESSION; LYSOSOMAL DEGRADATION; MEMBRANE FLUIDITY; MULTI-DRUG RESISTANCE