Department of Pharmacology, Medical School of Southeast University, Nanjing 210009, P.R. China.
Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing 210009, P.R. China.
J Microbiol Biotechnol. 2020 Dec 28;30(12):1835-1842. doi: 10.4014/jmb.2008.08019.
Ergosterol, an essential constituent of membrane lipids of yeast, is distributed in both the cell membrane and intracellular endomembrane components such as vacuoles. Honokiol, a major polyphenol isolated from , has been shown to inhibit the growth of . Here, we assessed the effect of honokiol on ergosterol biosynthesis and vacuole function in . Honokiol could decrease the ergosterol content and upregulate the expression of genes related with the ergosterol biosynthesis pathway. The exogenous supply of ergosterol attenuated the toxicity of honokiol against . Honokiol treatment could induce cytosolic acidification by blocking the activity of the plasma membrane Pma1p H-ATPase. Furthermore, honokiol caused abnormalities in vacuole morphology and function. Concomitant ergosterol feeding to some extent restored the vacuolar morphology and the function of acidification in cells treated by honokiol. Honokiol also disrupted the intracellular calcium homeostasis. Amiodarone attenuated the antifungal effects of honokiol against , probably due to the activation of the calcineurin signaling pathway which is involved in honokiol tolerance. In conclusion, this study demonstrated that honokiol could inhibit ergosterol biosynthesis and decrease Pma 1p H-ATPase activity, which resulted in the abnormal pH in vacuole and cytosol.
麦角甾醇是酵母膜脂的必需成分，分布于细胞膜和细胞内的内质网膜等成分中，如液泡。和厚朴酚是从厚朴中分离得到的主要多酚类化合物，已被证明能抑制的生长。在这里，我们评估了 honokiol 对麦角甾醇生物合成和液泡功能的影响。Honokiol 可以降低麦角甾醇含量并上调与麦角甾醇生物合成途径相关的基因的表达。麦角甾醇的外源供应可以减轻 honokiol 对的毒性。Honokiol 处理可通过阻断质膜 Pma1p H+-ATPase 的活性诱导胞质酸化。此外，honokiol 还会导致液泡形态和功能异常。同时添加麦角甾醇在一定程度上恢复了 honokiol 处理细胞的液泡形态和酸化功能。Honokiol 还破坏了细胞内钙稳态。胺碘酮减弱了 honokiol 对的抗真菌作用，可能是由于钙调神经磷酸酶信号通路的激活，该通路参与了 honokiol 的耐受性。总之，这项研究表明，honokiol 可以抑制麦角甾醇生物合成并降低 Pma1p H+-ATPase 的活性，从而导致液泡和胞质中 pH 值异常。
