School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Program), College of Natural Sciences, Kyungpook National University, Daegu, Korea.
FEMS Microbiol Lett. 2014 Jun;355(1):36-42. doi: 10.1111/1574-6968.12450. Epub 2014 May 13.
Melittin is one of the best-studied antimicrobial peptides, and many studies have focused on the membrane underlying its membrane-disruptive activity. We previously showed that melittin could cause some hallmarks of apoptosis in Candida albicans. Here, we first report the exact mechanism of melittin-induced fungal apoptosis. We first characterized the reactive oxygen species generated by melittin. The results showed that melittin strongly produced highly reactive hydroxyl radicals (˙OH), which contribute to cell death. Next, we showed that melittin also disrupted the mitochondrial membrane potential (ΔΨm) and induced the Ca(2+) release from the endoplasmic reticulum and its remarkable accumulation in mitochondria. Finally, we investigated the role of caspase in the apoptotic pathway. The results showed that melittin activated metacaspase, which was mediated by cytochrome c release. To summarize, melittin is involved in the mitochondria- and caspase-dependent apoptotic pathway in C. albicans. Our findings suggest that melittin possesses a dual antimicrobial mechanism, including membrane-disruptive and apoptotic actions.
蜂毒素是研究最为透彻的抗菌肽之一，许多研究都集中在其破坏细胞膜的活性的基础上。我们之前曾表明，蜂毒素可导致白色念珠菌出现一些细胞凋亡的特征。在这里，我们首次报道了蜂毒素诱导真菌凋亡的确切机制。我们首先对蜂毒素产生的活性氧进行了特征描述。结果表明，蜂毒素强烈产生高活性的羟自由基（˙OH），这有助于细胞死亡。接下来，我们表明蜂毒素还破坏了线粒体膜电位（ΔΨm），并诱导内质网中的 Ca(2+)释放及其在线粒体中的显著积累。最后，我们研究了半胱天冬酶在凋亡途径中的作用。结果表明，蜂毒素通过细胞色素 c 释放激活了效应半胱天冬酶。总之，蜂毒素参与了白色念珠菌中线粒体和半胱天冬酶依赖性的凋亡途径。我们的研究结果表明，蜂毒素具有双重抗菌机制，包括破坏细胞膜和诱导凋亡。
