Haq R U, Wereley J P, Chitambar C R
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA.
Exp Hematol. 1995 May;23(5):428-32.
It is known that iron is essential for cell growth and viability and that iron deprivation results in an inhibition in the synthesis of deoxyribonucleotides. However, steps leading to eventual cell death during iron deprivation are not fully understood. In the present study, we report that cellular iron-deficiency produced by exposure of human leukemic CCRF-CEM cells to gallium or the iron chelator deferoxamine (DFX) resulted in the inhibition of cell growth, condensation of chromatin, and the formation of DNA fragments (DNA-ladder), findings that are characteristic of apoptotic cell death. These effects of gallium and DFX were detected after a 48-hour incubation with cells and could be prevented by ferric ammonium citrate (FAC). Iron-deprivation produced a small increase in the endogenous expression of bcl-2 protein. Our studies provide additional information regarding the mechanism of cytotoxicity of gallium and DFX, and suggest, for the first time, a role for iron in the suppression of apoptotic cell death.
已知铁对于细胞生长和生存能力至关重要，且铁缺乏会导致脱氧核糖核苷酸合成受到抑制。然而，铁缺乏期间最终导致细胞死亡的具体步骤尚未完全明确。在本研究中，我们报告称，将人类白血病CCRF-CEM细胞暴露于镓或铁螯合剂去铁胺（DFX）所产生的细胞铁缺乏，导致细胞生长受到抑制、染色质凝聚以及DNA片段（DNA梯状条带）形成，这些发现是凋亡性细胞死亡的特征。镓和DFX的这些作用在与细胞孵育48小时后即可检测到，并且可被柠檬酸铁铵（FAC）阻止。铁缺乏使bcl-2蛋白的内源性表达略有增加。我们的研究提供了关于镓和DFX细胞毒性机制的更多信息，并首次表明铁在抑制凋亡性细胞死亡中发挥作用。
