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目的由于烟草烟雾中游离脂肪酸可与二价铁形成亲脂性复合物并输送铁到哺乳动物细胞,故其可能是重要的有毒成分。尽管早已发现这种铁负载增加了细胞膜不饱和脂肪酸氧化易感性,但脂肪酸:铁络合物的其他毒性所知甚少。方法利用酿酒酵母研究脂肪酸和铁的协同毒性和突变作用,同时观察了线粒体中脂肪酸介导铁沉积、脂质过氧化和活性氧产生。结果单纯铁和游离脂肪酸对酵母的活性及突变无明显影响,但二者联用有明显毒性。把酵母悬浮液在氮气中孵育可防止这种毒性,表明线粒体代谢生成的活性氧可能参与其中。呼吸缺陷酵母可对抗铁:脂肪酸诱导的毒性,具有增强铁储存能力的CCC1过表达酵母也有类似的保护作用。因维生素E或拉扎洛依(多不饱和脂肪酸过氧化反应抑制剂)可防止其杀伤作用,铁+脂肪酸的细胞毒性作用很可能是由膜多不饱和脂肪酸氧化损伤介导。结论铁:脂肪酸络合物所致铁超负荷的毒性作用可能涉及线粒体代谢。如果酵母中这些结果与吸烟相关的渐进性肺损伤有关,意味着烟草中看似无害的脂肪酸可能在微量“松散”铁存在情况下成为重要的有毒成分。
Purpose Since free fatty acids in tobacco smoke form lipophilic complexes with ferrous iron and deliver iron to mammalian cells, it may be an important toxic component. Although this iron load has long been found to increase susceptibility to oxidation of unsaturated fatty acids in cell membranes, little is known about other toxicities of fatty acids: iron complexes. Methods Saccharomyces cerevisiae was used to study the synergistic toxicity and mutation of fatty acids and iron. At the same time, fatty acid-mediated iron deposition, lipid peroxidation and reactive oxygen species generation in mitochondria were observed. Results Iron and free fatty acids had no significant effect on the activity and mutation of yeast, but the combination of them was obviously toxic. Incubation of the yeast suspension in nitrogen prevented this toxicity, suggesting that active oxygen generated by mitochondrial metabolism may be involved. Respiratory deficient yeasts have a similar protective effect against iron: fatty acid-induced toxicity, CCC1 overexpression yeast with enhanced iron storage capacity. Vitamin E or lazarol (a polyunsaturated fatty acid peroxidation inhibitor) can prevent its killing effect, and the cytotoxic effect of iron + fatty acid is likely to be mediated by the oxidative damage of membrane polyunsaturated fatty acids. Conclusion The toxic effects of iron overload on iron-fatty acid complexes may involve mitochondrial metabolism. If these results in yeast are linked to smoking-related progressive lung injury, it means that seemingly innocuous fatty acids in tobacco may be an important toxic component in the presence of trace amounts of “loose” iron.