Abstract
CaThi is a thionin-like peptide isolated from fruits of Capsicum annuum, which has strong antimicrobial activity against bacteria, yeasts and filamentous fungi, and induced reactive oxygen species (ROS) in fungi. ROS are molecules that appear in the early stages of programmed cell death or apoptosis in fungi. Due to this fact, in this work we analyzed some events that may be related to process of apoptosis on yeast induced by CaThi. To investigate this possibility, we evaluated phosphatidylserine (PS) externalization, presence of active caspases and the ability of CaThi to bind to DNA in Candida tropicalis cells. Additionally, we investigated mitochondrial membrane potential, cell surface pH, and extracellular H+ fluxes in C. tropicalis cells after treatment with CaThi. Our results showed that CaThi induced PS externalization in the outer leaflet of the cell membrane, activation of caspases, and it had the ability for DNA binding and to dissipate mitochondrial membrane potential. In addition, the cell surface pH increased significantly when the C. tropicalis cells were exposed to CaThi which corroborates with ~96% inhibition on extracellular H+ efflux. Taking together, these data suggest that this peptide is capable of promoting an imbalance in pH homeostasis during yeast cell death playing a modulatory role in the H+ transport systems. In conclusion, our results strongly indicated that CaThi triggers apoptosis in C. tropicalis cells, involving a pH signaling mechanism.
Highlights
Antimicrobial peptides (AMPs) are common molecules of the immune defense system in virtually all life forms, with representatives in organisms ranging from bacteria to plants and mammals [1,2,3]
Our results show an induction of caspase activity, suggesting a programmed cell death occurring by an apoptotic pathway (Figure 2)
Mitochondria play a crucial role in cell survival by generating ATP and controlling apoptosis, the cell cycle and other essential metabolisms
Summary
Antimicrobial peptides (AMPs) are common molecules of the immune defense system in virtually all life forms, with representatives in organisms ranging from bacteria to plants and mammals [1,2,3]. They participate in an ancient defense system, innate immunity, which is the first line of defense for most living organisms during the early stages of an infection [4,5].
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