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游离铁对血红蛋白热聚集的影响。

Effects of free soluble iron on thermal aggregation of hemoglobin.

机构信息

Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata 700064, India.

Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata 700064, India; Homi Bhabha National Institute, Mumbai 400094, India.

出版信息

Biophys Chem. 2021 Feb;269:106527. doi: 10.1016/j.bpc.2020.106527. Epub 2020 Dec 16.

Abstract

Aggregation of hemoglobin is implicated in the presentation of diseases like sickle cell disease and thalassemia. Hallmark of the disease being imbalance in the production of globin chains leading to aggregation of excess globin chains and aberrant hemoglobins associated with the disease, broadly categorized as hemoglobinopathy. We have studied thermal aggregation of hemoglobin at 70 °C and pH 6.5 using light scattering, flow cytometry and optical microscopy and tried to investigate effects of few abundant soluble metal ions on such aggregation. Our study indicate that only iron, both in Fe and Fe forms, could inhibit hemoglobin aggregation and the extent of inhibition was 60% in presence of 100 mgL FeCl. Similar effect was not seen in lysozyme aggregation. Metal ions such as, Cu, Zn and Ni also did not have any significant effects on hemoglobin aggregation. Results show this important chaperone like behavior of free iron affecting the kinetics and yield of the aggregation process which could have important consequence in the extent of severity of such hematological diseases.

摘要

血红蛋白的聚集与镰状细胞病和地中海贫血等疾病的发生有关。该病的特征是珠蛋白链的产生失衡,导致多余的珠蛋白链聚集和与疾病相关的异常血红蛋白,通常被归类为血红蛋白病。我们使用光散射、流式细胞术和光学显微镜研究了血红蛋白在 70°C 和 pH 6.5 下的热聚集,并试图研究几种丰富的可溶性金属离子对这种聚集的影响。我们的研究表明,只有铁(无论是 Fe 还是 Fe 形式)能够抑制血红蛋白的聚集,在存在 100mg/L FeCl 的情况下,抑制程度为 60%。在溶菌酶聚集中没有观察到类似的效果。像铜、锌和镍这样的金属离子对血红蛋白的聚集也没有任何显著影响。结果表明,游离铁的这种重要的伴侣样行为影响了聚集过程的动力学和产率,这可能对这些血液疾病的严重程度产生重要影响。

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