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Yin-Yang Mechanisms Regulating Lipid Peroxidation of Docosahexaenoic Acid and Arachidonic Acid in the Central Nervous System

机译:调节中枢二十二碳六烯酸和花生四烯酸脂过氧化的阴阳机制

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摘要

Phospholipids in the central nervous system (CNS) are rich in polyunsaturated fatty acids (PUFAs), particularly arachidonic acid (ARA) and docosahexaenoic acid (DHA). Besides providing physical properties to cell membranes, these PUFAs are metabolically active and undergo turnover through the “deacylation-reacylation (Land's) cycle”. Recent studies suggest a Yin-Yang mechanism for metabolism of ARA and DHA, largely due to different phospholipases A2 (PLA2s) mediating their release. ARA and DHA are substrates of cyclooxygenases and lipoxygenases resulting in an array of lipid mediators, which are pro-inflammatory and pro-resolving. The PUFAs are susceptible to peroxidation by oxygen free radicals, resulting in the production of 4-hydroxynonenal (4-HNE) from ARA and 4-hydroxyhexenal (4-HHE) from DHA. These alkenal electrophiles are reactive and capable of forming adducts with proteins, phospholipids and nucleic acids. The perceived cytotoxic and hormetic effects of these hydroxyl-alkenals have impacted cell signaling pathways, glucose metabolism and mitochondrial functions in chronic and inflammatory diseases. Due to the high levels of DHA and ARA in brain phospholipids, this review is aimed at providing information on the Yin-Yang mechanisms for regulating these PUFAs and their lipid peroxidation products in the CNS, and implications of their roles in neurological disorders.
机译:中枢神经系统(CNS)中的磷脂富含多不饱和脂肪酸(PUFA),尤其是花生四烯酸(ARA)和二十二碳六烯酸(DHA)。这些PUFA除了为细胞膜提供物理特性外,还具有代谢活性,并通过“脱酰-再酰化(Land's)循环”进行周转。最近的研究表明,主要是由于不同的磷脂酶A2(PLA2s)介导ARA和DHA的新陈代谢的阴阳机制。 ARA和DHA是环加氧酶和脂加氧酶的底物,可导致一系列脂质介体,它们具有促炎性和促分解作用。 PUFA易受氧自由基的过氧化作用,导致由ARA产生4-羟基壬烯醛(4-HNE)和由DHA产生4-羟基己烯醛(4-HHE)。这些烯类亲电试剂具有反应性,并能够与蛋白质,磷脂和核酸形成加合物。在慢性和炎性疾病中,这些羟基-烯基酮的感知到的细胞毒性和激素作用已经影响了细胞信号通路,葡萄糖代谢和线粒体功能。由于脑磷脂中DHA和ARA的含量很高,因此,本综述旨在提供有关调节中枢神经系统中这些PUFA及其脂质过氧化产物的阴阳机制的信息,以及它们在神经系统疾病中的作用。

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