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5-氨基酮戊酸对未诱导的弗氏红白血病细胞卟啉和血红蛋白合成的刺激作用

5-Aminolevulinic acid stimulation of porphyrin and hemoglobin synthesis by uninduced Friend erythroleukemic cells.

作者信息

Malik Z, Djaldetti M

出版信息

Cell Differ. 1979 Jun;8(3):223-33. doi: 10.1016/0045-6039(79)90049-6.

DOI:10.1016/0045-6039(79)90049-6
PMID:288514
Abstract

Porphyrin synthesis and iron accumulation was stimulated by exogenous 5-aminolevulinic acid (ALA) in uninduced Friend erythroleukemic cells (FELC). Uroporphyrin and protoporphyrin were the major intermediated precursors produced. All porphyrin types were conjugated to protein insoluble cellular components and could be extracted only by methanol sulfuric acid esterification. Heme content of the uninduced FELC was increased 6-fold in the presence of 5 x 10(-4) M ALA. As a consequence, the synthesis of the minor murine hemoglobin component was preferentially induced, an effect similar to that expressed by exogenous hemin. Addition of exogenous ALA to 0.5% DMSO-induced cells increased total hemoglobin synthesis with a higher efficiency of the minor hemoglobin. The endogenous synthesis of porphyrin from exogenous ALA was markedly reduced by hemin. Uroporphyrin, coproporphyrin, protoporphyrin and heme were equally repressed, indicating an inhibitory effect of hemin on ALA dehydrase and urosynthetase activities. In addition, hemin repressed [3H]leucine incorporation into protein by uninduced cells. Incubation of uninduced cells in culture medium without serum in the presence of hemin blocked their protein synthesis activity, whereas addition of serum exerted a protective effect on living FELC.

摘要

在未诱导的Friend红白血病细胞(FELC)中,外源性5-氨基乙酰丙酸(ALA)可刺激卟啉合成和铁蓄积。尿卟啉和原卟啉是产生的主要中间前体。所有类型的卟啉都与蛋白质不溶性细胞成分结合,且只能通过甲醇硫酸酯化来提取。在5×10⁻⁴ M ALA存在的情况下,未诱导的FELC的血红素含量增加了6倍。因此,优先诱导了小鼠次要血红蛋白成分的合成,这一效应与外源性血红素所表现的相似。向0.5%二甲基亚砜诱导的细胞中添加外源性ALA可增加总血红蛋白合成,且次要血红蛋白的合成效率更高。血红素可显著降低外源性ALA的内源性卟啉合成。尿卟啉、粪卟啉、原卟啉和血红素均受到同等程度的抑制,表明血红素对ALA脱水酶和尿卟啉合成酶活性具有抑制作用。此外,血红素可抑制未诱导细胞将[³H]亮氨酸掺入蛋白质中。在无血清的培养基中,在血红素存在的情况下培养未诱导细胞会阻断其蛋白质合成活性,而添加血清则对存活的FELC具有保护作用。

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