Delton-Vandenbroucke I, Grammas P, Anderson R E
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
J Lipid Res. 1997 Jan;38(1):147-59.
Docosahexaenoic acid (22:6n-3), an n-3 essential fatty acid derived from elongation and desaturation of linolenic acid (18:3n-3), is found in abundant proportion in the brain and the retina. It is generally assumed that the liver is the major source of 22:6n-3 for these organs, although some retinal and cerebral cells, such as retinal pigment epithelium (Wang and Anderson, 1993. Biochemistry. 32:13703-13709) and brain astrocytes (Moore et al. 1991. J. Neurochem. 56:518-524) have the ability to produce 22:6n-3. The aim of the present study was to determine whether retinal and cerebral microvascular endothelium could synthesize 22:6n-3. After incubation of both cultured bovine retinal and rat cerebral endothelial cells with [3-14C] 22:5n-3 in presence of serum, radioactivity was primarily recovered in 20:5n-3, indicating active retroconversion reactions in both tissues. However, 22:6n-3, 24:5n-3, and 24:6n-3 were also labeled. All of these metabolites were released in the medium as free fatty acids. Retinal endothelial cells preferentially released labeled 24-carbon metabolites, whereas cerebral endothelial cells released relatively more 20:5n-3 and 22:6n-3. With heat-inactivated serum or no serum, both endothelial cell preparations showed relatively higher retroconversion levels. However, in serum-deprived cells, the elongation/desaturation pattern was affected in retinal cells only, with an accumulation of 24:5n-3 relative to a decrease of 24:6n-3 and 22:6n-3. Fatty acid composition analyses revealed a decrease in long-chain polyunsaturated n-6 and n-3 fatty acids in retinal cells maintained in inactivated serum compared to normal serum, while no change was found in cerebral cells. Taken together, these results suggest that 1) the synthesis of 22:6n-3 by both retinal and cerebral endothelial cells is independent of a delta4-desaturase; 2) retinal and cerebral endothelia could be a source of 22:6n-3 for the retina and the brain, respectively; and 3) retinal endothelial delta6-desaturase, which converts 24:5n-3 to 24:6n-3, could be stimulated by serum components.
二十二碳六烯酸（22:6n-3）是一种n-3必需脂肪酸，由亚麻酸（18:3n-3）经延伸和去饱和作用衍生而来，在大脑和视网膜中含量丰富。一般认为，肝脏是这些器官中22:6n-3的主要来源，不过一些视网膜和大脑细胞，如视网膜色素上皮细胞（Wang和Anderson，1993年。《生物化学》。32:13703 - 13709）和大脑星形胶质细胞（Moore等人，1991年。《神经神经化学杂志》。56:518 - 524）有能力产生22:6n-3。本研究的目的是确定视网膜和大脑微血管内皮细胞是否能够合成22:6n-3。在血清存在的情况下，将培养的牛视网膜和大鼠大脑内皮细胞与[3-14C]22:5n-3一起孵育后，放射性主要在20:5n-3中回收，表明这两种组织中均存在活跃的逆转化反应。然而，22:6n-3、24:5n-3和24:6n-3也被标记。所有这些代谢产物均以游离脂肪酸的形式释放到培养基中。视网膜内皮细胞优先释放标记的24碳代谢产物，而大脑内皮细胞释放相对较多的20:5n-3和22:6n-3。使用热灭活血清或无血清时，两种内皮细胞制剂均显示出相对较高的逆转化水平。然而，在血清剥夺的细胞中，只有视网膜细胞的延伸/去饱和模式受到影响，相对于24:6n-3和22:6n-3的减少，24:5n-3积累。脂肪酸组成分析显示，与正常血清相比，在灭活血清中培养的视网膜细胞中长链多不饱和n-6和n-3脂肪酸减少，而大脑细胞中未发现变化。综上所述，这些结果表明：1）视网膜和大脑内皮细胞合成22:6n-3均不依赖于δ4-去饱和酶；2）视网膜和大脑内皮细胞可能分别是视网膜和大脑中22:6n-3的来源；3）将24:5n-3转化为24:6n-3的视网膜内皮δ6-去饱和酶可能受到血清成分的刺激。
