title: The antimicrobial peptide arenicin-1 promotes generation of reactive oxygen species and induction of apoptosis.
abstract: BACKGROUND
  Arenicin-1, a 21-residue antimicrobial peptide, is known to exert significant broad-spectrum antimicrobial activity without cytotoxicity in mammalian cells except at high concentration. However, the mechanism of fungal cell death by arenicin-1 is weakly understood.
  
  
  METHODS
  We confirmed an increase in reactive oxygen species (ROS) in Candida albicans exposed to arenicin-1 and investigated the apoptotic response to ROS accumulation using apoptosis detecting methods.
  
  
  CONCLUSIONS
  Cells exposed to arenicin-1 showed an increase in the production of ROS and cytotoxic hydroxyl radicals, which are the major factors of apoptosis. The increase in ROS was due to mitochondrial dysfunction caused by arenicin-1. We confirmed that arenicin-1 induced mitochondrial membrane depolarization and also triggered release of activated metacaspases. Further, it initiated an apoptotic mechanism acting on the plasma membrane, including plasma membrane depolarization and exposure of phosphatidylserine on the outer surface. Cells finally died, showing morphological changes in the nucleus and DNA structure. Based on these apoptotic phenomena induced by arenicin-1, we concluded that arenicin-1 exerts antifungal activity by inducing apoptosis.
  
  
  CONCLUSIONS
  This study suggests that the antimicrobial peptide arenicin-1 induces apoptosis in C. albicans via intracellular ROS accumulation and mitochondrial damage, resulting in fungal cell death.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sceinces, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701, Republic of Korea.
authors.forename: Jaeyong
authors.initials: J
authors.lastname: Cho
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015801:Helminth Proteins / Q000494:pharmacology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D015801:Helminth Proteins; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; C496888:arenicin-1, Arenicola marina