Glasgow W C, Eling T E
Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Arch Biochem Biophys. 1994 Jun;311(2):286-92. doi: 10.1006/abbi.1994.1239.
Epidermal growth factor induces the oxygenation of linoleic acid in Syrian hamster embryo fibroblasts, and the lipoxygenase-derived products potentiate the mitogenic signal. We have further characterized the linoleate metabolites of growth factor-activated cells by chiral phase HPLC analysis. The primary product was identified as the pure (S) enantiomer of 13-hydroxyoctadecadienoic acid (HODE). In comparison to 13(R)-HODE isomer, only the biologically derived 13(S)-HODE was active in augmenting DNA synthesis as assessed by [3H]thymidine incorporation. To extend these investigations, we defined the structural requirements of analogous lipid compounds necessary for stimulation of mitogenesis in these cells. Carbon-chain length, degree of unsaturation, type of oxidized functionality, position of oxygenated moiety, double-bond geometry, and chirality were all identified as factors that modulate the mitogenic activity of related compounds. The results demonstrate a high degree of specificity for (S)-isomer hydro(pero)xylinoleic acid metabolites in stimulating DNA synthesis and further define the relationship between linoleic acid metabolism and growth-factor-dependent cell growth.
表皮生长因子可诱导叙利亚仓鼠胚胎成纤维细胞中亚油酸的氧化，且脂氧合酶衍生的产物可增强有丝分裂信号。我们通过手性相高效液相色谱分析进一步对生长因子激活细胞的亚油酸代谢物进行了表征。主要产物被鉴定为13-羟基十八碳二烯酸（HODE）的纯（S）对映体。与13（R）-HODE异构体相比，通过[3H]胸苷掺入评估，只有生物来源的13（S）-HODE在增强DNA合成方面具有活性。为了扩展这些研究，我们确定了这些细胞中刺激有丝分裂所需的类似脂质化合物的结构要求。碳链长度、不饱和度、氧化官能团类型、含氧部分的位置、双键几何形状和手性均被确定为调节相关化合物有丝分裂活性的因素。结果表明，（S）-异构体氢（过）氧亚油酸代谢物在刺激DNA合成方面具有高度特异性，并进一步明确了亚油酸代谢与生长因子依赖性细胞生长之间的关系。
