TISSUE DISTRIBUTION AND CLEARANCE KINETICS OF NON-TRANSFERRIN-BOUND IRON IN THE HYPOTRANSFERRINEMIC MOUSE - A RODENT MODEL FOR HEMOCHROMATOSIS
TISSUE DISTRIBUTION AND CLEARANCE KINETICS OF NON-TRANSFERRIN-BOUND IRON IN THE HYPOTRANSFERRINEMIC MOUSE - A RODENT MODEL FOR HEMOCHROMATOSIS
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DOI：
10.1073/pnas.84.10.3457
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发表时间：
1987-05-01
影响因子：
11.1
通讯作者：
KAPLAN, J
中科院分区：
文献类型：
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作者：
CRAVEN, CM;ALEXANDER, J;KAPLAN, J
遗传性低转铁蛋白血症小鼠的铁在肝脏和胰腺中积累。患有遗传性血色素沉着症的人也会出现类似的组织铁积累模式。在这两种疾病中，脱铁转铁蛋白的血浆浓度降低。为了检验非转铁蛋白结合铁存在并被实质组织清除的假设，在缺乏脱铁转铁蛋白的动物中研究了 59Fe 的组织分布。使用两组动物：正常大鼠和通过静脉注射非放射性标记铁使转铁蛋白饱和的小鼠，以及患有先天性低转铁蛋白血症的小鼠。在对照动物中，注射的 59Fe 主要存在于骨髓和脾脏中。在转铁蛋白铁饱和的动物中，注射的59Fe在肝脏和胰腺中积累。低转铁蛋白血症或转铁蛋白铁饱和小鼠中胃肠道吸收的铁沉积在肝脏中。这表明新吸收的铁是从不与转铁蛋白结合的粘膜细胞中释放的。清除研究表明，转铁蛋白结合的 59Fe 在 50 分钟的半衰期内从大鼠循环中清除。在转铁蛋白铁饱和的动物中，注射的 59Fe 在半衰期 < 30 秒内被去除。通过聚丙烯酰胺凝胶电泳分析血清样品中 59Fe 的分布，证明存在未与转铁蛋白结合的 59Fe。这些结果证明了非转铁蛋白结合铁的存在和摄取系统。这些观察结果支持以下假设：实质铁超负荷是脱铁转铁蛋白浓度降低的结果。
Genetically hypotransferrinemic mice accumulate iron in the liver and pancreas. A similar pattern of tissue iron accumulation occurs in humans with hereditary hemochromatosis. In both disorders, there is a decreased plasma concentration of apotransferrin. To test the hypothesis that nontransferrin-bound iron exists and is cleared by the parenchymal tissues, the tissue distribution of 59Fe was studied in animals lacking apotransferrin. Two groups of animals were used: normal rats and mice whose transferrin had been saturated by an intravenous injection of nonradiolabeled iron, and mice with congenital hypotransferrinemia. In control animals, injected 59Fe was found primarily in the bone marrow and spleen. In the transferrin iron-saturated animals, injected 59Fe accumulated in the liver and pancreas. Gastrointestinally absorbed iron in hypotransferrinemic or transferrin iron-saturated mice was deposited in the liver. This indicates that newly absorbed iron is released from mucosal cells not bound to transferrin. Clearance studies demonstrated that transferrin-bound 59Fe was removed from the circulation of rats with a half-time of 50 min. In transferrin iron-saturated animals, injected 59Fe was removed with a half-time of < 30 s. Analysis of the distribution of 59Fe in serum samples by polyacrylamide gel electrophoresis demonstrated the presence of 59Fe not bound to transferrin. These results demonstrate the existence of and an uptake system for non-transferrin-bound iron. These observations support the hypothesis that parenchymal iron overload is a consequence of reduced concentrations of apotransferrin.