EFFECTS OF DIETARY VITAMIN-E ON THE BIOSYNTHESIS OF 5-LIPOXYGENASE PRODUCTS BY RAT POLYMORPHONUCLEAR LEUKOCYTES (PMNL)
EFFECTS OF DIETARY VITAMIN-E ON THE BIOSYNTHESIS OF 5-LIPOXYGENASE PRODUCTS BY RAT POLYMORPHONUCLEAR LEUKOCYTES (PMNL)
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DOI：
10.1016/0005-2760(89)90047-7
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发表时间：
1989-10-17
期刊：
影响因子：
--
通讯作者：
POWELL, WS
中科院分区：
文献类型：
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作者：
CHAN, AC;TRAN, K;POWELL, WS
多形核中性粒细胞（PMNL）的活化导致花生四烯酸通过磷脂酶A2从细胞磷脂中释放，并转化5-脂氧合酶途径的产物。迄今为止的证据表明，膳食维生素E（（R，R，R）-α-生育酚）可以影响环氧合酶和磷脂酶A2活性，并且这种维生素的作用是细胞/组织特异性的。本研究进行，以检查不同的饮食生育酚对PMNL生育酚含量和5-脂氧合酶的产品配置文件使用离子载体A23187作为兴奋剂在存在和不存在外源性花生四烯酸的影响。饲喂含有0、30或3000 ppm（R，R，R）-α-维生素E醋酸酯对断奶大鼠的17周导致PMNL维生素E的剂量相关富集。刺激PMNL会引起生育酚显着且快速的损失。当用A23187单独刺激PMNL时，5-HETE、LTB 4和19-羟基-LTB 4的合成与膳食生育酚浓度的增加成比例地降低。然而，当外源性花生四烯酸与A23187一起提供时，中等量的膳食生育酚（30 ppm）仍然抑制5-脂氧合酶产物的形成，但高剂量（3000 ppm）没有任何额外的抑制作用。在存在和不存在外源性花生四烯酸的情况下，对高浓度维生素E的这种差异反应高度表明，在这些浓度下，生育酚可能主要在底物释放水平起作用，而在较低浓度下，5-脂氧合酶被抑制。本研究的数据表明，PMNL中5-脂氧合酶产物形成的衰减可以通过膳食维生素E富集来实现。
Activation of polymorphonuclear neutrophils (PMNL) leads to the release of arachidonate from cellular phospholipids via a phospholipase A2, and conversion of products of the 5-lipoxygenase pathway. Evidence to date indicates the dietary vitamin E ((R,R,R)-.alpha.-tocopherol) can influence both cyclooxygenase and phospholipase A2 activities and that the effect of this vitamin is cell/tissue specific. The present study was undertaken in order to examine the effects of varying dietary tocopherol on PMNL tocopherol content and 5-lipoxygenase product profile using the ionophore A23187 as stimulant in the presence and absence of exogenous arachidonate. Feeding semi-purified diets containing 0, 30 or 3000 ppm of (R,R,R)-.alpha.-tocopherol acetate to weanling rats for 17 weeks resulted in a dose-related enrichment of PMNL tocopherol. Stimulation of PMNL elicited a significant and rapid loss of tocopherol. When PMNL were stimulated with A23187 alone, the synthesis of 5-HETE, LTB4 and 19-hydroxy-LTB4 was decreased in proportion to increasing dietary tocopherol concentrations. However, when exogenous arachidonate was provided with A23187, intermediate amounts of dietary tocopherol (30 ppm) still suppressed the formation of 5-lipoxygenase products, but high doses (3000 ppm) did not have any additional inhibitory effect. This differential response to high concentrations of vitamin E in the presence and absence of exogenous arachidonate highly suggest that at these concentrations, tocopherol may act principally at the level of substrate release whereas at lower concentrations, 5-lipoxygenase is inhibited. Data from this study demonstrated that attenuation of the formation of 5-lipoxygenase products in PMNL can be achieved by dietary vitamin E enrichment.