Lipid mediators in the neural cell nucleus: their metabolism, signaling, and association with neurological disorders.Neuroscientist 2009; 15(4):392-407N
Lipid mediators are important endogenous regulators of neural cell proliferation, differentiation, oxidative stress, inflammation, and apoptosis. They originate from enzymic degradation of glycerophospholipids, sphingolipids, and cholesterol by phospholipases, sphingomyelinases, and cytochrome P450 hydroxylases, respectively. Arachidonic acid-derived lipid mediators are called eicosanoids. Eicosanoids have emerged as key regulators of cell proliferation, differentiation, oxidative stress, and neuroinflammation. Another arachidonic acid-derived lipid mediator is lipoxin. Eicosanoids have proinflammatory effects, whereas lipoxins produce antiinflammatory effects. The crossponding lipid mediators of docosahexaenoic acid metabolism are named docosanoids. They include resolvins, protectins, and neuroprotectins. Docosanoids produce antioxidant, anti-inflammatory, and antiapoptotic effects in the brain tissue. Other glycerophospholipid-derived lipid mediators are platelet-activating factor, lysophosphatidic acid, and endocannabinoids. Degradation of sphingolipids also results in the generation of sphingolipid-derived lipid mediators. Sphingolipid-derived lipid mediators are ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. They mediate cellular differentiation, cell growth, and apoptosis. Similarly, cholesterol-derived lipid mediators hydroxycholesterol and oxycholesterol produce apoptosis. Most of these mediators originate from the plasma membrane. The nucleus has its own set of enzymes and lipid mediators that originate from the nuclear envelope and matrix. The purpose of this commentary is to describe basic and clinical information on lipid mediators in the nucleus.