Nolan R D, Danilowicz R M, Eling T E
Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Mol Pharmacol. 1988 Jun;33(6):650-6.
We have investigated the involvement of arachidonic acid release and metabolism in the mitogenic response, i.e., [3H]thymidine incorporation, to epidermal growth factor (EGF) in BALB/c 3T3 cells. EGF induces release of arachidonate and prostaglandin (PG) formation after its addition to BALB/c 3T3 cells at the same concentrations that stimulate mitogenesis. Further, EGF-stimulated mitogenesis is blocked by inhibitors of arachidonate metabolism including indomethacin, eicosatetraynoic acid, and dexamethasone, whereas the addition of major arachidonate products in BALB/c 3T3 cells, PGE2, PGF2 alpha, and their intermediates PGG2 and PGH2, stimulate mitogenesis in synergism with EGF. The addition of PGs to BALB/c 3T3 cells also overcame indomethacin- and eicosatetraynoic acid-inhibited responses to EGF. Indomethacin must be added with EGF in order to block arachidonate metabolism and subsequent mitogenesis. These results suggest that the release of arachidonic acid and its subsequent metabolism is an apparent early requirement for the initiation of cell cycle traversal by EGF.
我们研究了花生四烯酸的释放和代谢在BALB/c 3T3细胞对表皮生长因子（EGF）的促有丝分裂反应（即[3H]胸腺嘧啶核苷掺入）中的作用。在以刺激有丝分裂的相同浓度将EGF添加到BALB/c 3T3细胞后，EGF会诱导花生四烯酸的释放和前列腺素（PG）的形成。此外，花生四烯酸代谢抑制剂（包括吲哚美辛、二十碳四烯酸和地塞米松）可阻断EGF刺激的有丝分裂，而在BALB/c 3T3细胞中添加主要的花生四烯酸产物PGE2、PGF2α及其中间体PGG2和PGH2，则可与EGF协同刺激有丝分裂。向BALB/c 3T3细胞中添加PGs也克服了吲哚美辛和二十碳四烯酸对EGF的抑制反应。必须将吲哚美辛与EGF一起添加，才能阻断花生四烯酸代谢及随后的有丝分裂。这些结果表明，花生四烯酸的释放及其随后的代谢是EGF启动细胞周期进程的一个明显早期需求。
