Weber C, Aepfelbacher M, Lux I, Zimmer B, Weber P C
Institut für Prophylaxe und Epidemiologie, Kreislaufkrankheiten b.d. Universität Münichen, Munich, Germany.
Biochim Biophys Acta. 1991 Dec 3;1133(1):38-45. doi: 10.1016/0167-4889(91)90239-t.
We investigated the effects of different polyunsaturated fatty acids (PUFAs) of the n-6 and n-3 family on the PAF and LTD4 stimulated increase in cytosolic free Ca(2+)-concentration [Ca2+]i in retinoic acid (RA) differentiated, human monocytic U937 cells. Docosahexaenoic acid (10 microM DHA) reduced the PAF induced increase in [Ca2+]i from 455 +/- 25 nM to 319 +/- 24 nM (P less than 0.01). DHA also significantly attenuated the LTD4 induced increase in [Ca2+]. However [Ca2+]i-increase stimulated by f-MLP, ATP, or ionophore A 23187 was not affected by DHA. Other PUFAs like eicosapentaenoic acid (EPA), alpha-linolenic acid (LnA), arachidonic acid (AA) or gamma-linoleic acid (LA) were ineffective. Cellular differentiation as assessed by nitrobluetetrazolium reduction and enhanced expression of specific PAF binding sites in RA treated cells were not altered by DHA. Fatty acid composition in cellular phospholipids revealed effective incorporation of each PUFA. The DHA-effect on [Ca2+]i was time dependent and occurred at 48 h, whereas the DHA-content in phospholipids reached a plateau already at 24 h. The antioxidant vitamin E, the lipoxygenase inhibitor NDGA and the cytochrome P-450 inhibitor SKF 525A completely prevented the DHA induced reduction of PAF stimulated [Ca2+]i-increase. In contrast, the cyclooxygenase inhibitor indomethacin had no effect. Our results indicate that DHA selectively reduces intracellular [Ca2+]i-increases induced by PAF and LTD4 in RA-treated U937 cells, presumably involving an oxidative modification of DHA.
我们研究了 n-6 和 n-3 家族不同多不饱和脂肪酸（PUFA）对全反式维甲酸（RA）诱导分化的人单核细胞 U937 细胞中血小板活化因子（PAF）和白三烯 D4（LTD4）刺激引起的胞质游离钙浓度[Ca2+]i 升高的影响。二十二碳六烯酸（10μM DHA）可使 PAF 诱导的[Ca2+]i 升高从 455±25 nM 降至 319±24 nM（P<0.01）。DHA 还显著减弱了 LTD4 诱导的[Ca2+]升高。然而，f-MLP、ATP 或离子载体 A23187 刺激引起的[Ca2+]i 升高不受 DHA 影响。其他 PUFA，如二十碳五烯酸（EPA）、α-亚麻酸（LnA）、花生四烯酸（AA）或γ-亚麻酸（LA）则无效。通过硝基蓝四氮唑还原评估的细胞分化以及 RA 处理细胞中特异性 PAF 结合位点表达的增强均未因 DHA 而改变。细胞磷脂中的脂肪酸组成显示每种 PUFA 均有效掺入。DHA 对[Ca2+]i 的影响具有时间依赖性，在 48 小时出现，而磷脂中的 DHA 含量在 24 小时就已达到平台期。抗氧化剂维生素 E、脂氧合酶抑制剂 NDGA 和细胞色素 P-450 抑制剂 SKF 525A 完全阻止了 DHA 诱导的 PAF 刺激的[Ca2+]i 升高的降低。相反，环氧化酶抑制剂吲哚美辛则无作用。我们的结果表明，DHA 可选择性降低 RA 处理的 U937 细胞中 PAF 和 LTD4 诱导的细胞内[Ca2+]i 升高，这可能涉及 DHA 的氧化修饰。
