ALTERATIONS IN LIPID METABOLISM IN THE NERVOUS SYSTEM BY ETHANOL

这项研究的主要目的是阐明代谢功能。 神经组织中多不饱和脂肪酸和磷脂的含量 特别提到乙醇对它们的调节作用。在神经元中 膜，二十二碳六烯酸(22：6n3)是最丰富的 在磷脂中酯化的多不饱和脂肪酸。虽然22：6n3 被认为对正常的神经元和视网膜功能是必不可少的， 其重要性所涉及的确切机制尚不清楚。 然而，22：6n3的发布可能会发挥重要的作用 20：4N6在细胞信号转导中的作用被认为是由 胞浆磷脂酶A2(PLA2)。为了测试这种可能性， 我们检测了多不饱和脂肪酸的释放，22：6n3和 用大鼠脑突触体和C6胶质瘤从神经细胞膜中提取20：4N6 细胞。我们的研究表明，20：4N6优先被水解 通过内源性脂肪酶活性从大脑突触体中分离出来，尽管 突触体膜中22：6N3的丰度。这一版本不是 被低分子量磷脂酶A2或二酰甘油抑制剂阻断 (Dg)脂肪酶，但被胞浆中的PLA2抑制剂阻断，表明 PLA2活性可能主要参与其中。突触体22：6种 即使在受到刺激后也表现出对水解性的抵抗 多种激动剂，提示22：6N3作为膜成分 作为一种释放的游离脂肪酸，可能更具生理性 重要性。在大鼠的原代培养中也得到了类似的结果 海马神经元。与突触体脂肪酶活性相反， 胶质瘤细胞和原代培养的大鼠星形胶质细胞可降解20：4n6和 22：6n3在刺激和非刺激条件下都一样好， 表明缺乏特异性的。促进了22：6n3的发布 胶质细胞可能表明星形胶质细胞的支持作用之一可能是 向神经细胞膜提供22：6n3。

The principal objective of this study is to elucidate metabolic functions of polyunsaturated fatty acids and phospholipids in nervous tissues with particular reference to their modulation by ethanol. In neuronal membranes, docosahexaenoic acid (22:6n3) is the most abundant polyunsaturated fatty acid esterified in phospholipids. Although 22:6n3 is thought to be essential for proper neuronal and retinal function, the exact mechanisms involved in its essentiality are not clearly understood. It is possible, however, that the release of 22:6n3 may play an important role in cell signaling as has been suggested for 20:4n6 hydrolyzed by cytosolic phospholipase A2 (PLA2). In order to test this possibility, we have examined the release of polyunsaturated fatty acids, 22:6n3 and 20:4n6 from neuronal membranes using rat brain synaptosomes and C6 glioma cells. Our study indicated that 20:4n6 was preferentially hydrolyzed from brain synaptosomes by endogenous lipase activity, despite the high abundance of 22:6n3 in synaptosomal membranes. This release was not blocked by inhibitors for low molecular weight PLA2 or diacylglycerol (DG) lipase, but blocked by cytosolic PLA2 inhibitors, suggesting that PLA2 activity may be primarily involved. Synaptosomal 22:6 species appeared to be resistant to hydrolysis even after stimulation with various agonists, suggesting that 22:6n3 as a membrane component rather than as a released free fatty acid may be of more physiological importance. Similar results were obtained for primary cultures of rat hippocampal neurons. In contrast to the synaptosomal lipase activity, glioma cells and primary cultures of rat astroglia hydrolyzed 20:4n6 and 22:6n3 equally well under both stimulated and unstimulated conditions, indicating a lack of specificity. Facilitated release of 22:6n3 from glia cells may indicate that one of the supporting roles of astroglia may be providing 22:6n3 to neuronal membranes.