INHIBITION OF HEME-SYNTHESIS IN BONE-MARROW CELLS BY SUCCINYLACETONE - EFFECT ON GLOBIN-SYNTHESIS
INHIBITION OF HEME-SYNTHESIS IN BONE-MARROW CELLS BY SUCCINYLACETONE - EFFECT ON GLOBIN-SYNTHESIS
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DOI：
10.1002/jcb.240210201
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发表时间：
1983-01-01
影响因子：
4
通讯作者：
GOLDWASSER, E
中科院分区：
文献类型：
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作者：
BERU, N;SAHR, K;GOLDWASSER, E
在培养的大鼠骨髓细胞中研究了δ-氨基乙酰丙酸脱氢酶抑制剂4，6-二氧代庚酸（琥珀酰丙酮，SA）对总铁摄取、血红素合成和球蛋白合成的影响，以检查血红素和球蛋白合成的协调性。SA以剂量依赖性方式抑制对照和促红细胞生成素刺激细胞中的血红素合成;在10− 3 M时，抑制作用完全，而在10− 7 M时，没有显著影响。对总铁摄取的抑制也具有剂量依赖性，尽管在10− 3 M时并不完全。SA对血红素合成的抑制作用可通过加入10− 4 M的胆色素原或原卟啉IX部分克服。早在加入抑制剂后5小时，SA就几乎完全抑制了促红细胞生成素刺激和未刺激细胞中的珠蛋白形成。当血红素合成的抑制是不完全的，珠蛋白的合成被部分抑制。这些结果表明，血红素合成是促红细胞生成素介导的诱导培养的骨髓细胞中珠蛋白合成所必需的。
The effects of 4,6‐dioxoheptanoic acid (succinylacetone, SA), an inhibitor of δ‐aminolevulinic acid dehydratase, on total iron uptake, heme synthesis, and globin synthesis were studied in rat marrow cells in culture in order to examine the coordination of heme and globin synthesis. SA inhibited heme synthesis in both control and erythropoietin‐stimulated cells in a dose‐dependent fashion; at 10−3M, inhibition was complete, whereas at 10−7M, there was no significant effect. Inhibition of total iron uptake was also dose‐dependent although, at 10−3M, it was not complete. The inhibition of heme synthesis by SA was partially overcome by addition of 10−4M porphobilinogen or protoporphyrin IX. SA caused an almost complete suppression of globin formation in both erythropoietin‐stimulated and unstimulated cells as early as five hours after the addition of the inhibitor. When inhibition of heme synthesis was incomplete, globin synthesis was partially inhibited. These results indicate that heme synthesis is required for erythropoietin‐mediated induction of globin synthesis in cultured bone marrow cells.