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

The antimicrobial peptide arenicin-1 promotes generation of reactive oxygen species and induction of apoptosis
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DOI:
10.1016/j.bbagen.2011.08.011
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发表时间:
2011-12-01
影响因子:
3
通讯作者:
Lee, Dong Gun
Lee, Dong Gun
中科院分区:
生物学3区
文献类型:
--
作者:
Cho, Jaeyong;Lee, Dong Gun

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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.Results and 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.General significance: 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. (C) 2011 Elsevier B.V. All rights reserved.