Ethyl-EPA in Huntington disease—Potentially relevant mechanism of action

The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n − 3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing.     

Effects of cilostazol on lipid and fatty acid metabolism

Abstract Cilostazol is a selective inhibitor of phosphodiesterase III with anti-platelet-aggregatory and vasodilating properties. Randomised, double-blind, placebo-controlled trials in 2702 patients with intermittent claudication demonstrated that cilostazol significantly increased walking distances compared with placebo. Furthermore, the agent has beneficial effects on the serum lipid profile and fatty acid composition in plasma. Consequently, cilostazol may be useful to prevent atherosclerosis from progressing by ameliorating lipid and fatty acid metabolism.     

微藻异养产生二十碳五烯酸的新进展

二十碳五烯酸(Eicosapentaenoic acid简写EPA)是一种长链多不饱和脂肪酸，在营养强化、防治心血管疾病、减轻炎症等方面起着十分重要的作用。目前EPA主要来源于鱼油，很难满足市场对EPA日益增长的需求，必须寻求替代生产EPA的资源。一些微藻可在不需要光的条件下以廉价的有机物为原料异养生长，在异养条件下，可以很好地控制培养模式，有可能大规模地生产EPA。工业上用微藻生产EPA研究包括：筛选高EPA产量的微藻株，通过基因工程改善藻株，优化培养条件以及建立有效的培养体系。本文综述了近几年微藻在异养条件下生产EPA的最新进展，着重阐明硅藻是一种能在异养条件下生长且具有高EPA产率的模式藻株。     

多不饱和二十二碳六烯酸对白细胞介素-2α受体的抑制作用

目的：研究多不饱和二十二碳六烯酸(DHA)可通过改变IL-2a受体在细胞膜亚区域的分布和免疫抑制调节。方法：用DHA(22：6)处理Jurkat E6-1T细胞，硬脂酸(18：0)处理作为阴性对照。应用流式细胞仪检测DHA对T细胞表面分子CD25(IL-2Ra)表达的抑制作用。超速离心分离T细胞膜脂肪微区域，应用蛋白印迹法分析检测IL-2Ra所在的T细胞膜亚区域组分，与硬脂酸处理相比较，分析DHA处理对T细胞膜不同亚区域IL-2Ra分布的影响。结果：流式细胞仪检测表明，对照组75umol／L硬脂酸处理，检测到细胞表面CD25阳性表达细胞率为40．14％，75umol／LDHA处理T细胞，细胞表面CD25阳性表达细胞率为19．28％，DHA可抑制T细胞表面分子CD25的表达。蛋白印迹法分析确定IL-2Ra存在于rafts组分中，DHA处理使部分IL-2Ra从膜rafts区域移位到可溶膜区域。结论：膜脂肪微区域为IL-2受体信号转导的功能性亚区域，DHA通过调节IL-2Ra在膜脂肪微区域的分布，使部分IL-2Ra从功能性rafts区域移位到非功能性可溶膜区域，而产生免疫抑制作用。     

Polyunsaturated fatty acids balance affects platelet NOX2 activity in patients with liver cirrhosis

BackgroundNADPH-oxidase-2 up-regulation has been suggested in liver damage perpetuation via an oxidative stress-mediated mechanism. n-6/n-3 polyunsaturated fatty acids ratio derangement has been reported in liver disease.AimTo explore polyunsaturated fatty acids balance and its interplay with platelet oxidative stress in liver cirrhosis.MethodsA cross-sectional study in 51 cirrhotic patients and sex- and age-matched controls was performed. Serum polyunsaturated fatty acids and oxidative stress markers (urinary isoprostanes and serum soluble NADPH-oxidase-2-derived peptide) were measured. The effect on platelet oxidative stress of n-6/n-3 polyunsaturated fatty acids ratio in vitro and in vivo (1-week supplementation with 3 g/daily n-3-polyunsaturated fatty acids) was tested.ResultsCompared to controls, cirrhotic patients had significantly higher n-6/n-3 polyunsaturated fatty acids ratio. n-6/n-3 polyunsaturated fatty acids ratio correlated significantly with disease severity and oxidative stress markers. In vitro experiments showed that in Child–Pugh C patients’ platelets incubation with low n-6/n-3 polyunsaturated fatty acids ratio resulted in dose-dependent decrease of radical oxigen species (−39%), isoprostanes (−25%) and NADPH-oxidase-2 regulation (−51%). n-3 polyunsaturated fatty acids supplemented patients showed significant oxidative stress indexes reduction.ConclusionsIn cirrhosis, n-6/n-3 polyunsaturated fatty acids imbalance up-regulates platelet NADPH-oxidase-2 with ensuing oxidative stress. Further study to evaluate if n-3 supplementation may reduce disease progression is warranted.