SUBCELLULAR-DISTRIBUTION OF DESFERRIOXAMINE AND HYDROXYPYRIDIN-4-ONE CHELATORS IN K562 CELLS AFFECTS CHELATION OF INTRACELLULAR IRON POOLS
SUBCELLULAR-DISTRIBUTION OF DESFERRIOXAMINE AND HYDROXYPYRIDIN-4-ONE CHELATORS IN K562 CELLS AFFECTS CHELATION OF INTRACELLULAR IRON POOLS
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DOI：
10.1111/j.1365-2141.1993.tb03184.x
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发表时间：
1993-10-01
影响因子：
6.5
通讯作者：
PORTER, JB
中科院分区：
文献类型：
--
作者：
HOYES, KP;PORTER, JB
通过测量放射性标记的去铁胺 (DFO) 和口服活性羟基吡啶酮 (HPO) 螯合剂 1,2-二乙基-3-羟基吡啶-4-酮 (CP94) 的亚细胞分布，以及这些螯合剂改变铁的亚细胞分布的能力，检查了铁螯合剂与细胞内铁池的相互作用。 Fe-59 由受体介导的转铁蛋白内吞作用递送。 K562 细胞用 Fe-59 转铁蛋白脉冲，并用 DFO 或 CP94 (100 mum IBE) 攻击 20 或 240 分钟，然后进行亚细胞分级分离。 20 分钟时，用 CP94 孵育的细胞中溶酶体/颗粒 Fe-59（对照的 750%）和胞质 Fe-59 铁蛋白（对照的 50%）均显着降低 (P < 0.05)，这与用 DFO 处理的细胞不同，没有观察到降低。到 240 分钟。除此之外，CP94 还显着降低了细胞核、线粒体和低分子量胞质组分中 Fe-59 的积累（P < 0.05）。使用 DFO，仅在 240 分钟时观察到溶酶体/颗粒和胞质铁蛋白区室中的 Fe-59 显着降低（P < 0.05）。然而，此时，胞质低分子量 Fe-59 和胞质 DFO 均显着积累。与 DFO 相比，CP94 细胞内 Fe-59 的相对快速减少与 20 分钟时核、溶酶体/颗粒和低分子量胞质区室中 CP94 的积累显着高于 DFO 平行（P < 0.05）。这些结果表明，与 DFO 不同，转铁蛋白衍生的内体铁可能被 HPO 螯合。由于它们更快地被这些细胞器吸收。 HPO 比 DFO 更快地进入某些细胞内铁库，这可能解释了 HPO 抑制体内细胞增殖的可能性更大。
The interactions of iron chelators with intracellular iron pools have been examined by measuring the subcellular distribution of radiolabelled desferrioxamine (DFO) and the orally active hydroxypyridinone (HPO) chelator 1,2-diethyl-3-hydroxypyridin-4-one (CP94), as well as the ability of these chelators to modify the subcellular distribution of Fe-59 delivered by the receptor mediated endocytosis of transferrin. K562 cells were pulsed with Fe-59 transferrin and challenged with DFO or CP94 (100 mum IBE) for 20 or 240 min and then subjected to subcellular fractionation. At 20 min there was a significant decrease (P < 0.05) in both lysosomal/particulate Fe-59 (750% of control) and cytosolic Fe-59 ferritin (50% of control) in cells incubated with CP94, unlike cells treated with DFO where no decrease was observed. By 240 min. in addition to the above, Fe-59 accumulation was significantly decreased in the nuclear, mitochondrial, and low molecular weight cytosolic fractions with CP94 (P < 0.05). With DFO a significant decrease in Fe-59 in only the lysosomal/particulate and cytosolic ferritin compartments was observed at 240 min (P < 0.05). At this time, however, there was a significant accumulation of both cytosolic low molecular weight Fe-59 and cytosolic DFO. The relatively rapid decrease of Fe-59 within intracellular compartments seen with CP94 compared to DFO was paralleled by a significantly higher accumulation of CP94 than DFO in nuclear, lysosomal/particulate and low molecular weight cytosolic compartments at 20 min (P < 0.05). These results suggest that transferrin derived endosomal iron may be chelated by HPOs, unlike DFO. due to their faster uptake into these organelles. The more rapid access of HPOs than DFO to certain intracellular iron pools may explain the greater possibility of HPOs to inhibit proliferation of cells in vivo.