红细胞铁蛋白可减少细胞内铁蓄积、溶血和疟疾风险。
Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk.
机构信息
Section on Human Iron Metabolism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Science. 2018 Mar 30;359(6383):1520-1523. doi: 10.1126/science.aal2022.
Malaria parasites invade red blood cells (RBCs), consume copious amounts of hemoglobin, and severely disrupt iron regulation in humans. Anemia often accompanies malaria disease; however, iron supplementation therapy inexplicably exacerbates malarial infections. Here we found that the iron exporter ferroportin (FPN) was highly abundant in RBCs, and iron supplementation suppressed its activity. Conditional deletion of the gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. In humans, a prevalent mutation, Q248H (glutamine to histidine at position 248), prevented hepcidin-induced degradation of FPN and protected against severe malaria disease. Q248H appears to have been positively selected in African populations in response to the impact of malaria disease. Thus, FPN protects RBCs against oxidative stress and malaria infection.
疟原虫侵入红细胞（RBC），大量消耗血红蛋白，并严重扰乱人类的铁调节。贫血常伴有疟疾；然而，补铁治疗却莫名其妙地加剧了疟疾感染。在这里，我们发现铁输出蛋白 Ferroportin（FPN）在 RBC 中高度丰富，而铁补充会抑制其活性。在红细胞中条件性删除基因导致细胞内铁过量积累、细胞损伤、溶血，并增加感染疟原虫的小鼠的死亡率。在人类中，一种常见的突变 Q248H（第 248 位的谷氨酰胺突变为组氨酸）阻止了铁调素诱导的 FPN 降解，并可预防严重的疟疾疾病。Q248H 似乎在非洲人群中受到了积极选择，以应对疟疾疾病的影响。因此，FPN 可保护 RBC 免受氧化应激和疟疾感染。
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