The antimicrobial peptide arenicin-1 promotes generation of reactive oxygen species and induction of apoptosis. 2011

Jaeyong Cho, and Dong Gun Lee
School of Life Sciences and Biotechnology, College of Natural Sceinces, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701, Republic of Korea.

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.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D010718 Phosphatidylserines Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a SERINE moiety. Serine Phosphoglycerides,Phosphatidyl Serine,Phosphatidyl Serines,Phosphatidylserine,Phosphoglycerides, Serine,Serine, Phosphatidyl,Serines, Phosphatidyl
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000890 Anti-Infective Agents Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. Anti-Infective Agent,Anti-Microbial Agent,Antimicrobial Agent,Microbicide,Microbicides,Anti-Microbial Agents,Antiinfective Agents,Antimicrobial Agents,Agent, Anti-Infective,Agent, Anti-Microbial,Agent, Antimicrobial,Agents, Anti-Infective,Agents, Anti-Microbial,Agents, Antiinfective,Agents, Antimicrobial,Anti Infective Agent,Anti Infective Agents,Anti Microbial Agent,Anti Microbial Agents
D015801 Helminth Proteins Proteins found in any species of helminth. Helminth Protein,Protein, Helminth,Proteins, Helminth
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017382 Reactive Oxygen Species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS. Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
D023181 Antimicrobial Cationic Peptides Small cationic peptides that are an important component, in most species, of early innate and induced defenses against invading microbes. In animals they are found on mucosal surfaces, within phagocytic granules, and on the surface of the body. They are also found in insects and plants. Among others, this group includes the DEFENSINS, protegrins, tachyplesins, and thionins. They displace DIVALENT CATIONS from phosphate groups of MEMBRANE LIPIDS leading to disruption of the membrane. Cationic Antimicrobial Peptide,Cationic Antimicrobial Peptides,Cationic Host Defense Peptides,Host Defense Peptide,Microbicidal Cationic Proteins,Amphipathic Cationic Antimicrobial Peptides,Host Defense Peptides,Antimicrobial Peptide, Cationic,Antimicrobial Peptides, Cationic,Cationic Peptides, Antimicrobial,Cationic Proteins, Microbicidal,Defense Peptide, Host,Defense Peptides, Host,Peptide, Cationic Antimicrobial,Peptide, Host Defense,Peptides, Antimicrobial Cationic,Peptides, Cationic Antimicrobial,Peptides, Host Defense,Proteins, Microbicidal Cationic

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