Moraitou Marina, Dimitriou Evangelia, Dekker Nick, Monopolis Ioannis, Aerts Johannes, Michelakakis Helen
Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.
Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
Blood Cells Mol Dis. 2014 Jun-Aug;53(1-2):30-3. doi: 10.1016/j.bcmd.2014.01.005. Epub 2014 Feb 9.
Plasmalogens represent a unique class of phospholipids. Reduced red blood cell plasmalogen levels in Gaucher disease patients were reported, correlating to total disease burden. The relation between plasmalogen abnormalities in Gaucher disease patients and primary glycosphingolipid abnormalities, malonyldialdehyde levels, an indicator of lipid peroxidation, and the total antioxidant status was further investigated. Significant reduction of C16:0 and C18:0 plasmalogens in red blood cells of Gaucher disease patients was confirmed. In parallel, a significant increase in the glucosylceramide/ceramide ratio in red blood cell membranes, as well as an average 200-fold increase in plasma glucosylsphingosine levels was observed. Red blood cell malonyldialdehyde levels were significantly increased in patients, whereas their total antioxidant status was significantly reduced. A negative correlation between plasmalogen species and glucosylceramide, ceramide, glucosylceramide/ceramide ratio, glucosylsphingosine and malonyldialdehyde, significant for the C16:0 species and all the above parameters with the exception of malonyldialdehyde levels, was found along with a positive non-significant correlation with the total antioxidant status. Our results indicate that increased lipid peroxidation and reduced total antioxidant status exist in Gaucher disease patients. They demonstrate a clear link between plasmalogen levels and the primary glycolipid abnormalities characterizing the disorder and an association with the increased oxidative stress observed in Gaucher disease patients.
缩醛磷脂是一类独特的磷脂。据报道,戈谢病患者红细胞中的缩醛磷脂水平降低,这与疾病的总体负担相关。我们进一步研究了戈谢病患者缩醛磷脂异常与原发性糖鞘脂异常、丙二醛水平(脂质过氧化的指标)以及总抗氧化状态之间的关系。结果证实,戈谢病患者红细胞中C16:0和C18:0缩醛磷脂显著减少。与此同时,观察到红细胞膜中葡糖神经酰胺/神经酰胺比值显著升高,血浆葡糖鞘氨醇水平平均升高200倍。患者红细胞丙二醛水平显著升高,而其总抗氧化状态显著降低。我们发现缩醛磷脂种类与葡糖神经酰胺、神经酰胺、葡糖神经酰胺/神经酰胺比值、葡糖鞘氨醇和丙二醛之间存在负相关,对于C16:0种类以及除丙二醛水平外以上所有参数而言这种负相关均显著,同时与总抗氧化状态存在正相关但不显著。我们的研究结果表明,戈谢病患者存在脂质过氧化增加和总抗氧化状态降低的情况。研究结果表明缩醛磷脂水平与该疾病特征性的原发性糖脂异常之间存在明确联系,并且与戈谢病患者中观察到的氧化应激增加有关。