THE LDL RECEPTOR PATHWAY DELIVERS ARACHIDONIC-ACID FOR EICOSANOID FORMATION IN CELLS STIMULATED BY PLATELET-DERIVED GROWTH-FACTOR
THE LDL RECEPTOR PATHWAY DELIVERS ARACHIDONIC-ACID FOR EICOSANOID FORMATION IN CELLS STIMULATED BY PLATELET-DERIVED GROWTH-FACTOR
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DOI：
10.1038/345634a0
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发表时间：
1990-06-14
期刊：
影响因子：
64.8
通讯作者：
GLOMSET, JA
中科院分区：
文献类型：
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作者：
HABENICHT, AJR;SALBACH, P;GLOMSET, JA
动物细胞可以将20碳多不饱和脂肪酸转化为前列腺素（PC）和白三烯。这些局部产生的炎症和免疫反应介质以自分泌或旁分泌方式起作用1，2。花生四烯酸（AA）是大多数前列腺素和白三烯的前体，以脂酯的形式存在于血浆脂蛋白中，不能由动物细胞合成。因此，如果要形成PG或白三烯，必须向细胞提供AA或其植物来源的前体亚油酸2。由于几类脂蛋白，包括低密度脂蛋白（LDL）、极低密度脂蛋白和乳糜微粒残留物，通过LDL受体3 -5摄取，并且由于LDL和极低密度脂蛋白6 -8（而非高密度脂蛋白6）刺激PG合成，我们先前已经提出PG形成与LDL途径直接相关6。使用成纤维细胞与受体阴性表型的家族性高胆固醇血症和抗LDL受体抗体，我们在这里表明，LDL提供AA的PG生产和LDL受体依赖性反馈机制抑制活性的PGH合成酶，限速酶的PG合成。这些结果表明，低密度脂蛋白途径具有调节作用，PG合成，除了其众所周知的作用，在维持细胞胆固醇稳态。
ANIMAL cells can convert 20-carbon polyunsaturated fatty acids into prostaglandins (PCs) and leukotrienes. These locally produced mediators of inflammatory and immunological reactions act in an autocrine or paracrine fashion1,2. Arachidonic acid (AA), the precursor of most PGs and leukotrienes, is present in the form of lipid esters within plasma lipoproteins and cannot be synthesisedde novoby animal cells. Therefore, AA or its plant-derived precursor, linoleic acid, must be provided to cells if PGs or leukotrienes are to be formed2. Because several classes of lipoproteins, including low-density lipoproteins (LDL), very-low-density lipoproteins, and chylomicron remnants, are taken up by means of the LDL receptor3–5, and because LDL and very-low-density lipoproteins6–8, but not high-density lipoproteins6, stimulate PG synthesis, we have suggested previously that PG formation is directly linked to the LDL pathway6. Using fibroblasts with the receptor-negative phenotype of familial hypercholesterolaemia and anti-LDL receptor antibodies, we show here that LDL deliver AA for PG production and that an LDL receptor-dependent feedback mechanism inhibits the activity of PGH synthase, the rate-limiting enzyme of PG synthesis. These results indicate that the LDL pathway has a regulatory role in PG synthesis, in addition to its well-known role in the maintenance of cellular cholesterol homeostasis.