Nerol triggers mitochondrial dysfunction and disruption via elevation of Ca2+ and ROS in Candida albicans.
Nerol triggers mitochondrial dysfunction and disruption via elevation of Ca2+ and ROS in Candida albicans.
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DOI：
10.1016/j.biocel.2017.02.006
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
Jun Tian;Zhaoqun Lu;Yanzhen Wang;Man Zhang;Xueyan Wang;Xudong Tang;Xue Peng;H. Zeng
中科院分区：
文献类型：
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作者：
Jun Tian;Zhaoqun Lu;Yanzhen Wang;Man Zhang;Xueyan Wang;Xudong Tang;Xue Peng;H. Zeng
Nerol（NEL）对致病真菌白色念珠菌的抗真菌活性的最低抑制浓度（MIC）为4.4 mM，通过细胞凋亡样机制产生显着的杀念珠菌活性。细胞凋亡的主要原因是细胞内钙离子（Ca 2+）水平和活性氧（ROS）的产生。经NEL处理的白念珠菌细胞中，发现增加，这与线粒体功能障碍和破坏有关。用流式细胞仪和Western blot检测NEL引起的细胞凋亡的一系列特征性变化，包括线粒体膜去极化、细胞色素c（cyt c）释放和后半胱天冬酶（metacaspase）激活。结果表明，细胞内Ca 2+和ROS的增加导致线粒体膜电位（MMP）显著降低，细胞色素c也从线粒体释放到胞浆中。在后半胱天冬酶激活的情况下也观察到其他早期凋亡特征。采用Annexin V-FITC和PI双染、TUNEL法和DAPI染色观察细胞形态学变化，包括磷脂酰丝氨酸（PS）外化、核固缩和DNA断裂。结果支持NEL参与C.白细胞不仅在早期，而且在晚期也有。总之，NEL可通过升高Ca 2+和ROS引发线粒体功能障碍和破坏，从而导致细胞凋亡。白色念珠菌。本研究旨在探讨NEL对C.白色念珠菌的治疗具有重要意义。白色念珠菌感染。
The antifungal activity of Nerol (NEL) againstCandida albicans, a pathogenic fungus, has a minimum inhibitory concentration (MIC) of 4.4 mM that causes noteworthy candidacidal activity through an apoptosis-like mechanism. Calcium (Ca2+) levels and reactive oxygen species (ROS) production, which are the major causes of apoptosis, were determined inC. albicanscells treated with NEL and were found to increase, which related to mitochondrial dysfunction and disruption. A series of characteristic changes of apoptosis caused by NEL, including mitochondrial membrane depolarization, cytochrome c (cyt c) release, and metacaspase activation were examined using a flow cytometer and Western blot. The results showed that an increase in intracellular Ca2+and ROS led to dramatically decreased mitochondrial membrane potential (MMP); cyt c was also released from the mitochondria to the cytosol. Other early apoptotic features were also observed with the metacaspase activation. Finally, the morphological changes of the cells were observed, including phosphatidylserine (PS) externalization, nuclear condensation, and DNA fragmentation through Annexin V-FITC and PI double staining, TUNEL assay, and DAPI staining. The results supported the hypothesis that NEL was involved in the apoptosis ofC. albicanscells not only at the early stages, but also at the late stages. In summary, NEL can trigger mitochondrial dysfunction and disruption via elevation of Ca2+and ROS leading to apoptosis inC. albicans. This research on the mechanism of cell death triggered by NEL againstC. albicanshas important significance for providing a novel treatment ofC. albicansinfections.