CGA-N12, a peptide derived from chromogranin A, promotes apoptosis of Candida tropicalis by attenuating mitochondrial functions.
CGA-N12, a peptide derived from chromogranin A, promotes apoptosis of Candida tropicalis by attenuating mitochondrial functions.
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CGA-N12 是一种源自嗜铬粒蛋白 A 的肽，通过减弱线粒体功能促进热带念珠菌凋亡
DOI：
10.1042/bcj20170894
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发表时间：
2018-04-16
期刊：
影响因子：
--
通讯作者：
Chang J
中科院分区：
文献类型：
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作者：
Li R;Zhang R;Yang Y;Wang X;Yi Y;Fan P;Liu Z;Chen C;Chang J
CGA-N12（chromagranin A的N-末端的第65至第76位残基的氨基酸序列）是来源于人嗜铬粒蛋白A（CGA）的抗真菌肽。在我们之前的研究中，发现CGA-N12具有特异性抗念珠菌活性，尽管作用机制尚不清楚。在这里，我们研究了CGA-N12对线粒体的影响。我们发现CGA-N12诱导细胞内活性氧的过度产生和线粒体膜电位的耗散，前者在细胞凋亡的启动中起关键作用，后者是细胞凋亡的标志。因此，我们评估了用CGA-N12处理后热带念珠菌细胞的凋亡特征，发现如下：细胞色素c的泄漏和钙离子进入线粒体和细胞质的摄取;后半胱天冬酶激活;和凋亡表型，如染色质凝聚和DNA降解。结论CGA-N12能够诱导C. tropicalis细胞通过线粒体功能障碍和后半胱天冬酶激活。人CGA抗真菌肽CGA-N12作为抗真菌剂具有新的凋亡机制。
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.