title: Coprisin-induced antifungal effects in Candida albicans correlate with apoptotic mechanisms.
abstract: Coprisin is a 43-mer defensin-like peptide from the dung beetle, Copris tripartitus. Here, we investigated the induction of apoptosis by coprisin in Candida albicans cells. Coprisin exerted antifungal and fungicidal activity without any hemolytic effect. Confocal microscopy indicated that coprisin accumulated in the nucleus of cells. The membrane studies, 1,6-diphenyl-1,3,5-hexatriene, calcein-leakage, and giant unilamellar vesicle assays, confirmed that coprisin did not disrupt the fungal plasma membrane at all. Moreover, the activity of coprisin was energy- and salt-dependent. Next, we investigated whether coprisin induced apoptosis in C. albicans. Annexin V-FITC staining and TUNEL assay showed that coprisin was involved with both the early and the late stages of apoptosis. Coprisin also increased the intracellular reactive oxygen species level, and hydroxyl radicals were included at high levels among the species. The effect of thiourea as a hydroxyl radical scavenger further confirmed the existence of the hydroxyl radicals. Furthermore, coprisin induced mitochondrial membrane potential dysfunction, cytochrome c release, and activation of metacaspases. In summary, this study suggests that coprisin could be a model molecule for a large family of novel antimicrobial peptides possessing apoptotic activity.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Buk-gu, Daegu 702-701, Republic of Korea.
authors.forename: Juneyoung
authors.initials: J
authors.lastname: Lee
authors.forename: Jae-Sam
authors.initials: JS
authors.lastname: Hwang
authors.forename: In-Sok
authors.initials: IS
authors.lastname: Hwang
authors.forename: Jaeyong
authors.initials: J
authors.lastname: Cho
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.forename: Yangmee
authors.initials: Y
authors.lastname: Kim
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D023082:Defensins / Q000276:immunology; D004734:Energy Metabolism / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D007109:Immunity; D019476:Insect Proteins / Q000138:chemical synthesis / Q000494:pharmacology*; D013890:Thiourea / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D023082:Defensins; D016166:Free Radical Scavengers; D019476:Insect Proteins; C570442:coprisin peptide, Copris tripartitus; D013890:Thiourea