HYPOXIA AND THE TRANSCRIPTIONAL REGULATION OF CYP GENES IN CELLS

缺氧，或由细胞供血减少引起的缺氧，是心血管系统(如心绞痛或动脉粥样硬化)和许多其他器官(如癌症和化学介导的损伤)缺血性损伤的一个组成部分。现在已经知道，在细胞中，激活特定靶基因的某些蛋白质的含量会迅速增加，以应对缺氧。其中一些最重要的蛋白质是缺氧诱导因子-1(或HIF-1)和激活蛋白-1(或AP-1)。我们已经确定了一个新的靶基因，它在低氧中被激活。这种基因产生一种名为细胞色素P450 2J2的酶，它作用于细胞膜中存在的脂肪酸，并将它们转化为控制钾和钙离子流入细胞的分子。这些离子流入细胞的变化以前已经在低氧中观察到，但这种影响的机制尚不清楚。因此，细胞色素P450 2J2在缺氧时被激活，并产生控制细胞内保护性离子通量的脂肪酸代谢物。

Hypoxia, or oxygen deprivation caused by the decreased supply of blood to cells, is a component of ischaemic injury of the cardiovascular system (as in angina or atherosclerosis) and numerous other organs (e.g. in cancer and chemical-mediated injury). It is now known that the content of certain proteins that activate specialised target genes is increased rapidly in cells in response to oxygen deprivation. Some of the most important of these proteins are hypoxia-inducible factor-1 (or HIF-1) and activator protein-1 (or AP-1). We have identified a novel target gene that is activated in hypoxia. This gene produces an enzyme, termed cytochrome P450 2J2, that acts on fatty acids which are present in cell membranes and converts them into molecules that control the flow of potassium and calcium ions into cells. Alterations in the flow of such ions into cells have been observed previously in hypoxia but the mechanism of this effect is unclear. Thus, cytochrome P450 2J2 is switched on in hypoxia and generates fatty acid metabolites that control protective ion fluxes in cells.