Coccia E M, Profita V, Fiorucci G, Romeo G, Affabris E, Testa U, Hentze M W, Battistini A
Laboratorio di Virologia, Istituto Superiore di Sanità, Rome, Italy.
Mol Cell Biol. 1992 Jul;12(7):3015-22. doi: 10.1128/mcb.12.7.3015-3022.1992.
The mechanisms that regulate the expression of the H chain of the iron storage protein ferritin in Friend erythroleukemia cells (FLCs) after exposure to hemin (ferric protoporphyrin IX), protoporphyrin IX, and ferric ammonium citrate (FAC) have been investigated. Administration of hemin increases the steady-state level of ferritin mRNA about 10-fold and that of ferritin protein expression 20-fold. Experiments with the transcriptional inhibitor actinomycin D and transfection studies demonstrate that the increment in cytoplasmic mRNA content results from enhanced transcription of the ferritin H-chain gene and cannot be attributed to stabilization of preexisting mRNAs. In addition to transcriptional effects, translational regulation induces the recruitment of stored mRNAs into functional polyribosomes after hemin and FAC administration, resulting in a further increase in ferritin synthesis. Administration of protoporphyrin IX to FLCs produces divergent transcriptional and translational effects. It increases transcription but appears to suppress ferritin mRNA translation. FAC treatment increases the mRNA content slightly (about twofold), and the ferritin levels rise about fivefold over the control values. We conclude that in FLCs, hemin induces ferritin H-chain biosynthesis by multiple mechanisms: a transcriptional mechanism exerted also by protoporphyrin IX and a translational one, not displayed by protoporphyrin IX but shared with FAC.
研究了在暴露于血红素（铁卟啉 IX）、原卟啉 IX 和柠檬酸铁铵（FAC）后，调控铁储存蛋白铁蛋白重链在弗氏红白血病细胞（FLCs）中表达的机制。给予血红素可使铁蛋白 mRNA 的稳态水平增加约 10 倍，铁蛋白蛋白表达增加 20 倍。使用转录抑制剂放线菌素 D 的实验和转染研究表明，细胞质 mRNA 含量的增加是由于铁蛋白重链基因转录增强，而不能归因于已有 mRNA 的稳定。除了转录效应外，翻译调控在给予血红素和 FAC 后诱导储存的 mRNA 募集到功能性多核糖体中，导致铁蛋白合成进一步增加。向 FLCs 中给予原卟啉 IX 产生不同的转录和翻译效应。它增加转录，但似乎抑制铁蛋白 mRNA 的翻译。FAC 处理使 mRNA 含量略有增加（约两倍），铁蛋白水平比对照值升高约五倍。我们得出结论，在 FLCs 中，血红素通过多种机制诱导铁蛋白重链生物合成：原卟啉 IX 也发挥的转录机制和原卟啉 IX 未表现但与 FAC 共有的翻译机制。
