The antimicrobial peptide arenicin-1 promotes generation of reactive oxygen species and induction of apoptosis

• Published in: Biochimica et biophysica acta Vol. 1810; no. 12; pp. 1246 - 1251
• Main Authors: Cho, Jaeyong, Lee, Dong Gun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2011
• Subjects: Anti-Infective Agents - pharmacology; antifungal properties; Antimicrobial Cationic Peptides - pharmacology; antimicrobial peptides; Apoptosis; Apoptosis - drug effects; Arenicin-1; Candida albicans; cytotoxicity; DNA; fungi; Helminth Proteins - pharmacology; Humans; hydroxyl radicals; mammals; Membrane Potentials - drug effects; Mitochondrial damage; mitochondrial membrane; phosphatidylserines; Phosphatidylserines - metabolism; plasma membrane; Reactive oxygen species; Reactive Oxygen Species - metabolism; Candida albicans; Reactive oxygen species; TUNEL; DiBAC 4; ROS; Mitochondrial damage; DiOC 6; DAPI; Arenicin-1; DHR-123; HPF; Apoptosis
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2011.08.011

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. 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. 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. 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. ► Arenicin-1 increased ROS generation in C. albicans cells. ► Arenicin-1 may induce formation of hydroxyl radical. ► Arenicin-1 activates metacaspases in yeast. ► Arenicin-1 can induce apoptosis.