Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Int J Mol Sci. 2024 Oct 3;25(19):10672. doi: 10.3390/ijms251910672.
Neural membranes are composed of phospholipids, sphingolipids, cholesterol, and proteins. In response to cell stimulation or injury, the metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahexaenoic acid from the sn-2 position of the glycerol moiety by the action of phospholipases A. Arachidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotrienes, and thromboxane are also involved in cell proliferation, differentiation, blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell protective effects. Sphingolipid-derived metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes, including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hydroxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage.
神经膜由磷脂、鞘脂、胆固醇和蛋白质组成。在细胞受到刺激或损伤时，脂质代谢会产生各种脂质介质，从而发挥许多细胞功能。因此，磷脂酶 A 作用于甘油部分的 sn-2 位，从磷脂中释放出花生四烯酸或二十二碳六烯酸。花生四烯酸是前列腺素、白三烯、血栓素和脂氧素的前体。在这些介质中，前列腺素、白三烯和血栓素会引发神经炎症。相比之下，脂氧素则具有抗炎和促修复作用。前列腺素、白三烯和血栓素还参与细胞增殖、分化、凝血和血管通透性。而 DHA 衍生的脂质介质则被称为特异性促修复脂质代谢物（SPM）。它们包括 resolvins、protectins 和maresins。这些介质通过产生抗炎、促修复和细胞保护作用来调节免疫功能。鞘脂衍生的代谢物包括神经酰胺、神经酰胺 1-磷酸、鞘氨醇和鞘氨醇 1 磷酸。它们调节许多细胞过程，包括酶活性、细胞迁移和黏附、炎症和免疫。胆固醇代谢为羟基胆固醇和 7-酮胆固醇，不仅破坏膜流动性，还促进炎症、氧化应激和细胞凋亡。这些过程导致细胞损伤。
