Postoak D, Nystuen L, King L, Ueno M, Beckman B S
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Am J Physiol. 1990 Dec;259(6 Pt 1):C849-53. doi: 10.1152/ajpcell.1990.259.6.C849.
The role of specific products of the lipoxygenase pathway of arachidonic acid metabolism has been investigated in the Friend erythroleukemia cell line, a model system for erythroid cell differentiation. When triggered with agents such as hexamethylene-bis-acetamide, these cells mature as normal erythroid cells. 15-Hydroxyeicosatetraenoic acid (15-HETE) was identified by reverse-phase high-performance liquid chromatography and by radioimmunoassay as the principal lipoxygenase metabolite produced by Friend cells. Its production was significantly lower (903 +/- 73 pg/ml) in stationary-phase cells compared with logarithmic-phase cells (1,496 +/- 24 pg/ml). In addition, inhibitors of both the cyclooxygenase and lipoxygenase pathways (phenidone, BW 755C, caffeic acid, nordihydroguaiaretic acid and BW 4AC) significantly blocked DNA synthesis (P less than 0.05), whereas neither specific inhibitor of the cyclooxygenase pathway (aspirin or sodium meclofenate) blocked DNA synthesis. The addition of 15-hydroperoxyeicosatetraenoic acid as well as 15-HETE to Friend cells produced an increase in DNA synthesis as assessed by [3H]thymidine incorporation in differentiating cells but not in proliferating cells. These data support a role for 15-lipoxygenase products of arachidonic acid metabolism in maintaining DNA synthesis.
花生四烯酸代谢的脂氧合酶途径的特定产物在弗氏红白血病细胞系（一种红系细胞分化的模型系统）中的作用已得到研究。当用六亚甲基双乙酰胺等试剂触发时，这些细胞会正常成熟为红系细胞。通过反相高效液相色谱法和放射免疫测定法，鉴定出15-羟基二十碳四烯酸（15-HETE）是弗氏细胞产生的主要脂氧合酶代谢产物。与对数期细胞（1496±24 pg/ml）相比，静止期细胞中其产量显著降低（903±73 pg/ml）。此外，环氧化酶和脂氧合酶途径的抑制剂（非那吡啶、BW 755C、咖啡酸、去甲二氢愈创木酸和BW 4AC）显著阻断DNA合成（P<0.05），而环氧化酶途径的特异性抑制剂（阿司匹林或甲氯芬那酸钠）均未阻断DNA合成。通过在分化细胞而非增殖细胞中掺入[3H]胸腺嘧啶来评估，向弗氏细胞中添加15-氢过氧化二十碳四烯酸以及15-HETE会使DNA合成增加。这些数据支持花生四烯酸代谢的15-脂氧合酶产物在维持DNA合成中发挥作用。
