title: Nerol triggers mitochondrial dysfunction and disruption via elevation of Ca2+and ROS in Candida albicans.
abstract: The antifungal activity of Nerol (NEL) against Candida albicans, a pathogenic fungus, has a minimum inhibitory concentration (MIC) of 4.4mM 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 in C. albicans cells 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 of C. albicans cells 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 in C. albicans. This research on the mechanism of cell death triggered by NEL against C. albicans has important significance for providing a novel treatment of C. albicans infections.
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; Key Laboratory for New Drug Research of TCM and Shenzhen Branch, State R&D Centre for Viro-Biotech, Research Institute of Tsinghua University in Shenzhen, Shenzhen, 518057, Guangdong, PR China; Key Laboratory of Protection and Utilization of Biological Resources, College of Life Science, Tarim University, Alar, 843300, Xinjiang, PR China. Electronic address: tj-085@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China.
authors.forename: Zhaoqun
authors.initials: Z
authors.lastname: Lu
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China.
authors.forename: Yanzhen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory for New Drug Research of TCM and Shenzhen Branch, State R&D Centre for Viro-Biotech, Research Institute of Tsinghua University in Shenzhen, Shenzhen, 518057, Guangdong, PR China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory for New Drug Research of TCM and Shenzhen Branch, State R&D Centre for Viro-Biotech, Research Institute of Tsinghua University in Shenzhen, Shenzhen, 518057, Guangdong, PR China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Tang
authors.affiliation: College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Peng
authors.affiliation: Key Laboratory of Protection and Utilization of Biological Resources, College of Life Science, Tarim University, Alar, 843300, Xinjiang, PR China. Electronic address: zenghong0705@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zeng
mesh_terms: D000080462:Acyclic Monoterpenes; D000935:Antifungal Agents / Q000494:pharmacology; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D000080462:Acyclic Monoterpenes; D000935:Antifungal Agents; D017382:Reactive Oxygen Species; D013729:Terpenes; C007836:geraniol; D002118:Calcium
keywords: Antifungal; Apoptosis; Calcium; Candida albicans; Nerol; Reactive oxygen species