Han Giyeol, Lee Dong Gun
School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, South Korea.
IUBMB Life. 2022 Mar;74(3):235-244. doi: 10.1002/iub.2579. Epub 2021 Nov 25.
Indole propionic acid (IPA) which majorly influences the modulation of cellular respiration is a metabolite generated by gut microbiota. The antimicrobial effects of IPA have not been previously demonstrated. Therefore, this study focused on investigating the antimicrobial activity of IPA. Initially, antifungal activity of IPA against Candida albicans was observed, accompanied by variations in mitochondrial respiration indicating modulation of NAD /NADH ratios. Consumption of O contributes to the respiratory regulation and triggered by Ca overloading. After treatment with IPA, the cells were monitored, and Ca increases leading to membrane depolarization and reactive oxygen species (ROS) accumulation in mitochondria were noted. Depolarization of mitochondria membrane induced release of proapoptotic proteins in mitochondria. Oxidative stress exerted by ROS contributed to glutathione depletion and oxidation of glutathione (GSH). Fragmentation of DNA is a characteristic event leading to apoptosis and accompanies major hallmarks of apoptosis including phosphatidylserine exposure and metacaspase activation. In addition, phosphatidylserine exposure and metacaspase activation were detected in the cell treated with IPA. In conclusion, IPA triggered apoptosis in C. albicans under the influence of Ca .
吲哚丙酸（IPA）是一种由肠道微生物群产生的代谢产物，主要影响细胞呼吸的调节。IPA的抗菌作用此前尚未得到证实。因此，本研究着重于探究IPA的抗菌活性。最初，观察到IPA对白色念珠菌具有抗真菌活性，同时线粒体呼吸发生变化，表明NAD/NADH比率受到调节。氧气的消耗有助于呼吸调节，并由钙超载引发。用IPA处理细胞后，对细胞进行监测，发现钙增加导致线粒体膜去极化和活性氧（ROS）积累。线粒体膜去极化诱导线粒体中促凋亡蛋白的释放。ROS施加的氧化应激导致谷胱甘肽耗竭和谷胱甘肽（GSH）氧化。DNA片段化是导致细胞凋亡的一个特征性事件，并伴随着细胞凋亡的主要标志，包括磷脂酰丝氨酸暴露和metacaspase激活。此外，在用IPA处理的细胞中检测到了磷脂酰丝氨酸暴露和metacaspase激活。总之，在钙的影响下，IPA触发了白色念珠菌的细胞凋亡。
