Key Lab of Science & Technology of Eco-textile, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, China.
Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Beijing, People's Republic of China.
Free Radic Res. 2020 Apr;54(4):231-243. doi: 10.1080/10715762.2020.1751151. Epub 2020 Apr 16.
Amphotericin B has been the gold standard for the treatment of invasive mycosis for many years. Its resistance mechanisms are reported to be mainly related to the decrease of ergosterol content or the changes of cell wall. Previous study has shown that strain lack of was sensitive significantly to Amphotericin B. In the present study, the role of on Amphotericin B resistance were investigated. We found that enhanced the resistance of yeast cells to Amphotericin B, which was not related to cellular ergosterol content. can maintain the permeability of mitochondrial membrane and cell membrane integrity by inhibiting the accumulation of intercellular reactive oxygen species and alleviating the production of lipid peroxidation and superoxide radical. These alterations were attributed to the enhancement of the activities of superoxide dismutase, catalase and glutathione peroxidase, and the increased glutathione content. Taken together, inhibits oxidative damage induced by Amphotericin B through increasing activities of antioxidant enzymes and levels of GSH to alleviate the accumulation of reactive oxygen species, lipid peroxidation and superoxide radical, resulting in the maintenance of mitochondrial membrane potential and cell membrane integrity. However, Amphotericin B resistance mediated by is independent of Yap1p, GSH1 and Hog1p. The results demonstrate for the first time that enhances cell resistance to Amphotericin B by inhibiting oxidative damage in yeast. Our findings improve current understanding of the mechanism of Amphotericin B resistance and provide potential strategy for reducing Amphotericin B resistance.
两性霉素 B 多年来一直是治疗侵袭性真菌感染的金标准。其耐药机制主要与麦角固醇含量降低或细胞壁变化有关。先前的研究表明，缺乏 的 菌株对两性霉素 B 明显敏感。在本研究中，研究了 对两性霉素 B 耐药性的作用。我们发现 增强了酵母细胞对两性霉素 B 的耐药性，这与细胞麦角固醇含量无关。 通过抑制细胞内活性氧的积累和缓解脂质过氧化和超氧自由基的产生， 可以维持线粒体膜和细胞膜的完整性。这些变化归因于超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性的增强以及谷胱甘肽含量的增加。综上所述， 通过增加抗氧化酶的活性和 GSH 的水平来抑制由两性霉素 B 引起的氧化损伤，从而减轻活性氧、脂质过氧化和超氧自由基的积累，维持线粒体膜电位和细胞膜的完整性。然而， 通过 介导的两性霉素 B 耐药性与 Yap1p、GSH1 和 Hog1p 无关。研究结果首次表明， 通过抑制酵母中的氧化损伤来增强细胞对两性霉素 B 的耐药性。我们的研究结果提高了对两性霉素 B 耐药性机制的理解，并为降低两性霉素 B 耐药性提供了潜在策略。
