Laub R, Schneider Y J, Octave J N, Trouet A, Crichton R R
Biochem Pharmacol. 1985 Apr 15;34(8):1175-83. doi: 10.1016/0006-2952(85)90492-7.
Two radiolabelled derivatives of deferrioxamine B (DF) have been synthesized: methyl-DF and acetyl-DF. Both derivatives are non cytotoxic and stable in cell culture but they are degraded in human plasma and more extensively in rat plasma. Methyl-DF, acetyl-DF and DF mobilize radioiron to the same extent from hepatocytes loaded with 59Fe citrate in the same range of extracellular concentrations. The uptake and release of the 3H-labelled derivatives and their corresponding iron complexes have been measured and appear to represent a passive phenomenon resulting from the gradient of concentration between the cellular compartment and the extracellular medium. The results indicate that only a limited pool of cellular iron is accessible for chelation and that neither the permeability of the cellular membrane, nor the intracellular concentration of the chelators are the limiting factors for iron mobilization. On the basis of the subcellular distribution of the 3H-DF analogues, methylamine inhibition of iron chelation by siderophores in cell cultures and the positive effect of acidic pH and hydrolysis by lysosomal enzymes on in vitro iron mobilization from radiolabelled ferritin, we suggest that iron mobilization by DF and its derivatives occurs in lysosomes where they complex iron released from ferritin under the conjugate actions of acidic pH and lysosomal enzymes.
已合成去铁胺B（DF）的两种放射性标记衍生物：甲基-DF和乙酰-DF。这两种衍生物均无细胞毒性，在细胞培养中稳定，但在人血浆中会降解，在大鼠血浆中降解更广泛。在相同的细胞外浓度范围内，甲基-DF、乙酰-DF和DF从负载柠檬酸铁59的肝细胞中动员放射性铁的程度相同。已测量了3H标记衍生物及其相应铁络合物的摄取和释放，这似乎是由细胞内区室与细胞外介质之间的浓度梯度导致的一种被动现象。结果表明，只有有限的细胞内铁池可用于螯合，细胞膜的通透性和螯合剂的细胞内浓度都不是铁动员的限制因素。基于3H-DF类似物的亚细胞分布、细胞培养中甲基胺对铁载体铁螯合的抑制作用以及酸性pH和溶酶体酶水解对放射性标记铁蛋白体外铁动员的积极作用，我们认为DF及其衍生物的铁动员发生在溶酶体中，在酸性pH和溶酶体酶的共同作用下，它们与从铁蛋白释放的铁形成络合物。
