Labile iron, ROS, and cell death are prominently induced by haemin, but not by non-transferrin-bound iron
Labile iron, ROS, and cell death are prominently induced by haemin, but not by non-transferrin-bound iron
复制标题
DOI：
10.1016/j.transci.2021.103319
复制
发表时间：
2022-04-01
影响因子：
1.9
通讯作者：
Saigo, Katsuyasu
中科院分区：
文献类型：
--
作者：
Imoto, Shion;Sawamura, Tohru;Saigo, Katsuyasu
背景：在输血相关的铁超载中，单核/巨噬细胞中的血源性铁积累是初始事件。当铁负荷超过铁蛋白储存能力时，铁被释放到血浆中。当铁负荷超过转铁蛋白结合能力时，出现不稳定的非转铁蛋白结合铁（NTBI）并引起器官损伤。haemin诱导的细胞死亡已经被研究过；然而，NTBI是否诱导单核/巨噬细胞死亡尚不清楚。材料和方法：人单核THP-1细胞用haemin或NTBI处理，特别是柠檬酸铁铵（FAC）或硫酸亚铁铵（FAS）。用铁敏感荧光探针测定细胞内不稳定铁池（LIP）。western blotting检测铁蛋白表达。结果：血凝素治疗后LIP升高，FAC和FAS治疗后无升高。血红蛋白处理后活性氧（ROS）的产生和细胞死亡诱导显著，而FAC和FAS处理后则无显著差异。铁蛋白的表达在FAC和haemin处理之间没有差异。铁螯合剂和铁下垂抑制剂的联合使用显著增强了对血细胞毒性的抑制（p = 0.011）。讨论：LIP的差异表明血源性铁和NTBI的铁运输机制不同。铁螯合剂与抗氧化剂的结合有利于铁超载治疗。
Background: In transfusion-related iron overload, haem-derived iron accumulation in monocytes/macrophages is the initial event. When iron loading exceeds the ferritin storage capacity, iron is released into the plasma. When iron loading exceeds transferrin binding capacity, labile, non-transferrin-bound iron (NTBI) appears and causes organ injury. Haemin-induced cell death has already been investigated; however, whether NTBI induces cell death in monocytes/macrophages remains unclear.Material and Methods: Human monocytic THP-1 cells were treated with haemin or NTBI, particularly ferric ammonium citrate (FAC) or ferrous ammonium sulfate (FAS). The intracellular labile iron pool (LIP) was measured using an iron-sensitive fluorescent probe. Ferritin expression was measured by western blotting.Results: LIP was elevated after haemin treatment but not after FAC or FAS treatment. Reactive oxygen species (ROS) generation and cell death induction were remarkable after haemin treatment but not after FAC or FAS treatment. Ferritin expression was not different between the FAC and haemin treatments. The combination of an iron chelator and a ferroptosis inhibitor significantly augmented the suppression of haemin cytotoxicity (p = 0.011).Discussion: The difference in LIP suggests the different iron traffic mechanisms for haem-derived iron and NTBI. The Combination of iron chelators and antioxidants is beneficial for iron overload therapy.