Institute of Bioanalysis, Faculty of Medicine, University of Pécs, Pécs, Hungary.
Food Chem Toxicol. 2013 Sep;59:636-42. doi: 10.1016/j.fct.2013.07.006. Epub 2013 Jul 11.
Citrinin (CTN) is a toxic fungal metabolite that is a hazardous contaminant of foods and feeds. In the present study, its acute toxicity and effects on the plasma membrane of Schizosaccharomyces pombe were investigated. The minimum inhibitory concentration of CTN against the yeast cells proved to be 500 μM. Treatment with 0, 250, 500 or 1000 μM CTN for 60 min resulted in a 0%, 2%, 21% or 100% decrease, respectively, in the survival rate of the cell population. Treatment of cells with 0, 100, 500 or 1000 μM CTN for 20 min induced decrease in the phase-transition temperature of the 5-doxylstearic acid-labeled plasma membrane to 16.51, 16.04, 14.18 or 13.98°C, respectively as measured by electron paramagnetic resonance spectroscopy. This perturbation was accompanied by the efflux of essential K⁺ from the cells. The existence of an interaction between CTN and glutathione was detected for the first time by spectrofluorometry. Our observations may suggest a direct interaction of CTN with the free sulfhydryl groups of the integral proteins of the plasma membrane, leading to dose-dependent membrane fluidization. The change in fluidity disturbed the ionic homeostasis, contributing to the death of the cells, which is a novel aspect of CTN cytotoxicity.
桔青霉素（CTN）是一种有毒的真菌代谢物，是食品和饲料中有害的污染物。在本研究中，研究了其对裂殖酵母质膜的急性毒性和影响。CTN 对酵母细胞的最小抑制浓度被证明为 500μM。用 0、250、500 或 1000μM CTN 处理 60 分钟，分别导致细胞群体存活率下降 0%、2%、21%或 100%。用 0、100、500 或 1000μM CTN 处理细胞 20 分钟，用电子顺磁共振波谱法测量，标记的 5-二氧辛基硬脂酸标记的质膜的相变温度分别降低到 16.51、16.04、14.18 或 13.98°C。这种扰动伴随着必需 K⁺从细胞中流出。首次通过荧光光谱法检测到 CTN 与谷胱甘肽之间存在相互作用。我们的观察结果可能表明 CTN 与质膜整合蛋白的游离巯基基团直接相互作用，导致膜流动性依赖性。这种流动性的变化扰乱了离子的动态平衡，导致细胞死亡，这是 CTN 细胞毒性的一个新方面。
