Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, Thailand.
Blood Cells Mol Dis. 2012 Feb 15;48(2):77-85. doi: 10.1016/j.bcmd.2011.11.004. Epub 2011 Dec 7.
Hemoglobin H disease (Hb H) arises through the loss or dysfunction of three of the four alpha globin genes through the co-inheritance of either gross gene deletions or an abnormal hemoglobin which causes a non-deletional loss of α-globin expression. This study sought to investigate erythropoiesis in Hb H-Constant Spring (Hb H-CS) disease, a common form of Hb H disease in Southeast Asia, caused by the inheritance of the Constant Spring variant hemoglobin together with deletion of two of the alpha globin genes. In comparison to normal erythroblasts, Hb H-CS erythroblasts showed reduced cell expansion although no difference in differentiation was observed. Proteomic analysis revealed the increased expression of both chaperone and chaperonin proteins as well as down regulation of proteins regulating apoptosis. Both chaperone and chaperonin mediated folding require ATP, and evidence of increase energy demand was seen in the form of increased expression of enzymes involved in purine biosynthesis and increased levels of reactive oxygen species. A significant increase in apoptosis was seen in Hb H-CS erythroblasts, and the results from the proteomic analysis suggest that this arises at least in part from the consequences of increased folding requirements in the Hb H-CS erythroblast.
血红蛋白 H 病（Hb H）是由于四条α珠蛋白基因中的三条丢失或功能丧失而导致的，其通过两种机制共同遗传，一种是大片段基因缺失，另一种是异常血红蛋白导致的α-珠蛋白表达非缺失性丧失。本研究旨在探讨血红蛋白 H-Constant Spring（Hb H-CS）病（东南亚常见的一种血红蛋白 H 病）的红细胞生成情况，这种疾病是由 Constant Spring 变异血红蛋白的遗传和两个α珠蛋白基因的缺失引起的。与正常红细胞相比，Hb H-CS 红细胞的细胞扩张减少，尽管在分化方面没有差异。蛋白质组学分析显示，伴侣蛋白和伴侣素蛋白的表达增加，以及调节细胞凋亡的蛋白表达下调。伴侣蛋白和伴侣素介导的折叠都需要 ATP，并且可以通过参与嘌呤生物合成的酶的表达增加和活性氧水平的增加来证明能量需求的增加。Hb H-CS 红细胞的凋亡明显增加，蛋白质组学分析的结果表明，这至少部分是由于 Hb H-CS 红细胞折叠需求增加的结果。
