Ponka P, Grady R W, Wilczynska A, Schulman H M
Biochim Biophys Acta. 1984 Dec 20;802(3):477-89. doi: 10.1016/0304-4165(84)90367-2.
The chelating agent pyridoxal isonicotinoyl hydrazone (PIH) has recently been shown to mobilize 59Fe from reticulocytes loaded with non-heme 59Fe. In this study, various chelating agents were tested for their ability to effect the mobilization of iron from reticulocytes by PIH. They fall into several groups. The largest group includes chelators such as citrate, ethylenediaminetetracetic acid and desferrioxamine, which fail to affect PIH-induced iron mobilization and do not mobilize iron per se. Either these chelators do not enter reticulocytes or they do not take up iron from PIH-Fe complexes. The second group includes chelators such as 2,2'-bipyridine, 1,10-phenanthroline, bathophenanthroline sulfonate and N,N'-ethylenebis(o-hydroxyphenylglycine) which inhibit PIH-induced iron mobilization from reticulocytes and, when added together with PIH, induce radioiron accumulation in an alcohol-soluble fraction of reticulocytes. It appears that these chelators enter the cell and compete with PIH for 59Fe(II), but having bound iron are unable to cross the cell membrane. Spectral analysis suggests that Fe(II) chelators such as 2,2'-bipyridine and 1,10-phenanthroline remove iron from Fe(II)PIH but are not able to do so from Fe(III)PIH. Then there are compounds such as 2,3-dihydroxybenzoic acid and catechol which potentiate PIH-induced iron mobilization although they are unable to mobilize iron from reticulocytes by themselves. Lastly, there is a group of miscellaneous compounds which include chelators that either potentiate the iron-mobilizing effect of PIH as well as mobilizing iron from reticulocytes by themselves (tropolone), or that reduce PIH-induced iron mobilization while themselves having an iron-mobilizing effect (N,N'-bis(2,3-dihydroxybenzoyl)-1,6-diaminohexane). In further experiments, heme was found to stimulate globin synthesis in reticulocytes, the heme synthesis of which was inhibited by PIH, suggesting that PIH is probably not toxic to the cells.
螯合剂吡啶醛异烟酰腙（PIH）最近已被证明能从负载非血红素59Fe的网织红细胞中动员59Fe。在本研究中，测试了各种螯合剂通过PIH影响网织红细胞中铁动员的能力。它们可分为几组。最大的一组包括柠檬酸盐、乙二胺四乙酸和去铁胺等螯合剂，它们不会影响PIH诱导的铁动员，本身也不会动员铁。这些螯合剂要么不进入网织红细胞，要么不从PIH-Fe复合物中摄取铁。第二组包括2,2'-联吡啶、1,10-菲咯啉、磺酸基邻菲咯啉和N,N'-亚乙基双（邻羟基苯甘氨酸）等螯合剂，它们抑制PIH诱导的网织红细胞铁动员，当与PIH一起添加时，会在网织红细胞的醇溶性部分诱导放射性铁积累。似乎这些螯合剂进入细胞并与PIH竞争59Fe（II），但结合铁后无法穿过细胞膜。光谱分析表明，2,2'-联吡啶和1,10-菲咯啉等Fe（II）螯合剂能从Fe（II）PIH中去除铁，但不能从Fe（III）PIH中去除铁。然后还有2,3-二羟基苯甲酸和儿茶酚等化合物，它们增强了PIH诱导的铁动员，尽管它们本身无法从网织红细胞中动员铁。最后，有一组杂类化合物，其中包括既能增强PIH的铁动员作用又能自身从网织红细胞中动员铁的螯合剂（托酚酮），或者能降低PIH诱导的铁动员同时自身具有铁动员作用的化合物（N,N'-双（2,3-二羟基苯甲酰基）-1,6-二氨基己烷）。在进一步的实验中，发现血红素能刺激网织红细胞中的珠蛋白合成，而其血红素合成受到PIH的抑制，这表明PIH可能对细胞无毒。
