The physiological functions of iron regulatory proteins in iron homeostasis - an update.
The physiological functions of iron regulatory proteins in iron homeostasis - an update.
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DOI：
10.3389/fphar.2014.00124
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发表时间：
2014
影响因子：
5.6
通讯作者：
Rouault TA
中科院分区：
文献类型：
--
作者：
Zhang DL;Ghosh MC;Rouault TA
铁调节蛋白（IRP）通过与靶mRNA中称为铁响应元件（IRE）的RNA茎环结构结合来调节参与铁代谢的基因的表达。IRP结合抑制转录本5 ′非翻译区含有IRE的mRNA的翻译，并增加转录本3 ′非翻译区含有IRE的mRNA的稳定性。通过这些机制，IRP增加细胞铁吸收并减少铁的储存和输出，以维持最佳的细胞内铁平衡。哺乳动物IRP蛋白家族有两个成员，IRP1和IRP2，它们具有冗余的功能，如完全缺乏IRP表达的小鼠（Irp1-/-/Irp2-/-小鼠）的胚胎致死性所证明的，这与Irp1-/-和Irp2-/-小鼠存活的事实形成对比。此外，Irp2-/-小鼠也表现出神经退行性症状和小细胞低色素性贫血，表明IRP2功能在神经系统和红细胞生成稳态中占主导地位。虽然自20世纪90年代初首次评估Irp1-/-动物以来，IRP1的生理意义尚不清楚，但最近的研究表明，IRP1在协调红细胞生成和身体铁稳态之间的平衡方面发挥着重要作用。此外，Irp1-/-小鼠发展为肺动脉高压，并且当维持缺铁饮食时，它们经历猝死，这表明IRP1在肺和心血管系统中具有关键作用。本文综述了IRP1和IRP2的生理作用，并进一步讨论了其对特发性红细胞增多症、肺动脉高压和神经退行性变患者的临床研究意义。
Iron regulatory proteins (IRPs) regulate the expression of genes involved in iron metabolism by binding to RNA stem-loop structures known as iron responsive elements (IREs) in target mRNAs. IRP binding inhibits the translation of mRNAs that contain an IRE in the 5′untranslated region of the transcripts, and increases the stability of mRNAs that contain IREs in the 3′untranslated region of transcripts. By these mechanisms, IRPs increase cellular iron absorption and decrease storage and export of iron to maintain an optimal intracellular iron balance. There are two members of the mammalian IRP protein family, IRP1 and IRP2, and they have redundant functions as evidenced by the embryonic lethality of the mice that completely lack IRP expression (Irp1-/-/Irp2-/- mice), which contrasts with the fact that Irp1-/- and Irp2-/- mice are viable. In addition, Irp2-/- mice also display neurodegenerative symptoms and microcytic hypochromic anemia, suggesting that IRP2 function predominates in the nervous system and erythropoietic homeostasis. Though the physiological significance of IRP1 had been unclear since Irp1-/- animals were first assessed in the early 1990s, recent studies indicate that IRP1 plays an essential function in orchestrating the balance between erythropoiesis and bodily iron homeostasis. Additionally, Irp1-/- mice develop pulmonary hypertension, and they experience sudden death when maintained on an iron-deficient diet, indicating that IRP1 has a critical role in the pulmonary and cardiovascular systems. This review summarizes recent progress that has been made in understanding the physiological roles of IRP1 and IRP2, and further discusses the implications for clinical research on patients with idiopathic polycythemia, pulmonary hypertension, and neurodegeneration.
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影响因子：
29
作者：
Anderson SA;Nizzi CP;Chang YI;Deck KM;Schmidt PJ;Galy B;Damnernsawad A;Broman AT;Kendziorski C;Hentze MW;Fleming MD;Zhang J;Eisenstein RS
通讯作者：
Eisenstein RS
DOI：
10.1096/fj.10-177378
发表时间：
2011-06
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Formenti F;Beer PA;Croft QP;Dorrington KL;Gale DP;Lappin TR;Lucas GS;Maher ER;Maxwell PH;McMullin MF;O'Connor DF;Percy MJ;Pugh CW;Ratcliffe PJ;Smith TG;Talbot NP;Robbins PA
通讯作者：
Robbins PA
影响因子：
20.3
作者：
Chua, ACG;Olynyk, JK;Trinder, D
通讯作者：
Trinder, D
影响因子：
4.8
作者：
Chung, Jacky;Anderson, Sheila A.;Paw, Barry H.
通讯作者：
Paw, Barry H.
影响因子：
20.3
作者：
Ferring-Appel, Dunja;Hentze, Matthias W.;Galy, Bruno
通讯作者：
Galy, Bruno