Inhibition of dimethyl sulfoxide-stimulated Friend cell erythrodifferentiation by hydrocortisone and other steroids.
Inhibition of dimethyl sulfoxide-stimulated Friend cell erythrodifferentiation by hydrocortisone and other steroids.
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氢化可的松和其他类固醇抑制二甲亚砜刺激的弗兰德细胞红细胞分化。
DOI：
10.1073/pnas.75.8.3851
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发表时间：
1978
影响因子：
11.1
通讯作者：
C. Friend
中科院分区：
文献类型：
--
作者：
W. Scher;D. Tsuei;S. Sassa;P. Price;N. Gabelman;C. Friend
二甲基亚砜刺激的Friend红白血病细胞的红细胞分化和血红蛋白合成被氢化可的松（HC）和其他四种类固醇激素：地塞米松，脱氧皮质酮，皮质酮和醛固酮抑制。该效应是特异性的，因为在抑制浓度下，这些化合物中的任何一种均未发生显著的细胞毒性。对HC的作用机理进行了详细的研究。在不存在二甲基亚砜的情况下，它对血红蛋白水平没有影响;但是，在存在这种诱导剂的情况下，血红素和球蛋白的合成分别被抑制约90%。通过细胞裂解物的凝胶电泳测定，除珠蛋白外，任何主要蛋白质的合成均无改变。血红素生物合成途径中的两种酶，δ-氨基乙酰丙酸酯酶和尿卟啉原-I合酶的活性分别被抑制80%和70%。珠蛋白mRNA诱导减少约90%。这表明HC对珠蛋白合成的抑制发生在翻译前步骤。二甲基亚砜诱导的DNA单链断裂，已被认为在朋友白血病细胞分化中发挥作用，数量减少，但没有消除。HC将二甲基亚砜刺激病毒释放到培养基中的作用降低了约50%。在不存在二甲基亚砜的情况下，HC处理使病毒产量加倍。
Erythrodifferentiation and hemoglobin synthesis in dimethyl sulfoxide-stimulated Friend erythroleukemia cells were inhibited by hydrocortisone (HC) and four other steroids: dexamethasone, deoxycorticosterone, corticosterone, and aldosterone. The effect was specific, because no significant cytotoxicity occurred with any of these compounds at the concentrations that were inhibitory. The mechanism of action of HC was studied in detail. In the absence of dimethyl sulfoxide, it had no effect on hemoglobin levels; but, in the presence of this inducer, the synthesis of heme and globin were each inhibited by approximately 90%. There was no alteration in the synthesis of any major protein other than globin, as determined by gel electrophoresis of cell lysates. The activities of two enzymes in the heme biosynthetic pathway, delta-aminolevulinate dehydratase and uroporphyrinogen-I synthase, were inhibited by 80% and 70%, respectively. Globin mRNA induction was reduced by approximately 90%. This demonstrated that the HC inhibition of globin synthesis occurred at a pretranslational step. The dimethyl sulfoxide-induced single-stranded breaks in DNA, which have been suggested to play a role in Friend leukemia cell differentiation, were reduced in number but not eliminated. HC reduced the dimethyl sulfoxide-stimulation of virus release into the medium by approximately 50%. HC treatment in the absence of dimethyl sulfoxide doubled the production of virus.