CGA-N12, a peptide derived from chromogranin A, promotes apoptosis of Candida tropicalis by attenuating mitochondrial functions.
Rui Fang LiRuiling ZhangYanhui YangXueqin WangYanjie YiPei FanZhengwei LiuChen ChenJunpeng ChangPublished in: The Biochemical journal (2018)
CGA-N12 (the amino acid sequence from the 65th to the 76th residue of the N-terminus of chromagranin A) is an antifungal peptide derived from human chromogranin A (CGA). In our previous investigation, CGA-N12 was found to have specific anti-candidal activity, though the mechanism of action remained unclear. Here, we investigated the effects of CGA-N12 on mitochondria. We found that CGA-N12 induced an over-generation of intracellular reactive oxygen species and dissipation in mitochondrial membrane potential, in which the former plays key roles in the initiation of apoptosis and the latter is a sign of the cell apoptosis. Accordingly, we assessed the apoptosis features of Candida tropicalis cells after treatment with CGA-N12 and found the following: leakage of cytochrome c and uptake of calcium ions into mitochondria and the cytosol; metacaspase activation; and apoptotic phenotypes, such as chromatin condensation and DNA degradation. In conclusion, CGA-N12 is capable of inducing apoptosis in C. tropicalis cells through mitochondrial dysfunction and metacaspase activation. Antifungal peptide CGA-N12 from human CGA exhibits a novel apoptotic mechanism as an antifungal agent.
Keyphrases
- cell cycle arrest
- cell death
- oxidative stress
- candida albicans
- induced apoptosis
- reactive oxygen species
- endoplasmic reticulum stress
- pi k akt
- endothelial cells
- amino acid
- gene expression
- cell proliferation
- biofilm formation
- transcription factor
- single molecule
- induced pluripotent stem cells
- risk assessment
- quantum dots
- genome wide