杂合子β地中海贫血骨髓中珠蛋白链合成失衡
Imbalanced globin chain synthesis in heterozygous beta-thalassemic bone marrow.
作者信息
Chalevelakis G, Clegg J B, Weatherall D J
出版信息
Proc Natl Acad Sci U S A. 1975 Oct;72(10):3853-7. doi: 10.1073/pnas.72.10.3853.
Abstract
Globin synthesis was studied in the bone marrow of seven heterozygous beta-thalassemic subjects. We found evidence of significant imbalance of alpha- and beta-chain production particularly at short times of incubation. There was a progressive decrease in alpha/beta-chain production ratio with increasing incubation time which was due to a decreased rate of net alpha-chain production, indicating that a large proportion of the newly synthesized alpha chains are degraded, particularly in bone marrow, within a few minutes of synthesis, leading to relatively low alpha/beta ratios if these are measured solely at incubation times greater than 10 min. The significant degradation of excess alpha chains explains why inclusion body formation and ineffective erythropoiesis, notable in beta-thalassemia homozygotes where there is gross chain imbalance, are not observed to any marked degree in heterozygotes.
摘要
对7名杂合子β地中海贫血患者的骨髓中的珠蛋白合成进行了研究。我们发现α链和β链产生存在显著失衡的证据，尤其是在孵育时间较短时。随着孵育时间的增加，α/β链产生比率逐渐降低，这是由于净α链产生速率下降所致，表明新合成的α链中有很大一部分在合成后几分钟内就被降解了，尤其是在骨髓中。如果仅在孵育时间大于10分钟时进行测量，就会导致相对较低的α/β比率。过量α链的显著降解解释了为什么在杂合子中未观察到明显程度的包涵体形成和无效红细胞生成，而在β地中海贫血纯合子中存在严重的链失衡时，这些现象较为明显。
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