Heavy Dietary Iron Loading Reduced IRE-Binding Activities of Iron Regulatory Proteins in Rat liver

高鐵餵飼降低大鼠肝臟鐵調節蛋白的IRE結合活性

何素珍(Su-Chen He) ； 蕭寧馨(Ning-Sing Shaw)

《中華民國營養學會雜誌》 28卷3期 (2003/09) Pp. 148-157

https://doi.org/10.6691/JCNS.200309_28(3).0005

摘要

鐵調節蛋白(iron regulatory proteins 1 and 2， IRPs)藉由與特定mRNA上的IRE(iron responsive element)結合，影響某些蛋白質的表現，例如：鐵蛋白、運鐵蛋白受體及粒線體aconitase等，進而調節鐵的貯存、獲取及利用，維持細胞鐵的恆定。細胞培養實驗顯示加鐵會使IRP1插入鐵硫聚集轉變為細胞質aconitase，失去與IRE結合的能力，但是不會改變IRP1蛋白質的量。另一方面，鐵會加速IRP2蛋白質的降解作用，進而降低其與IRE結合的量。本實驗的目的乃是探討餵飼高鐵飼料對大鼠肝臟IRPs活性的影響，並觀察鐵蛋白的表現是否受IRPs/IRE系統調控。十二隻離乳SD品系雄鼠，隨機分為二組，分別餵予正常(37mg/kg Fe)及高鐵(2.5% carbonyl iron；25，000 mg/kg Fe)飼料８週，犧牲取樣進行分析。結果發現，高鐵餵飼會使得大鼠肝臟堆積大量的鐵，IRPs的自發性IRE結合活性顯著降低，鐵蛋白表現增加，符合目前已知的調控機制。

關鍵字

鐵調節蛋白 ； 高鐵 ； 鐵蛋白 ； 大鼠

並列摘要

Iron regulatory proteins (IRPs)-1 and -2 regulate the synthesis of proteins involved in iron homeostasis through binding to the iron-responsive element (IRE) in the putative mRNA. In cell culture, the iron supplement converts IRPl to the inactive IRE-binding form-cytosolic aconitase, by inserting an iron-sulfur cluster without changing the protein level. In contrast to IRP 1, iron inactivates IRP 2 by promoting its degradation. In addition to examining the effect of a dietary iron overload on the hepatic IRE-binding activities of IRPs in an animal and to determine if the IRPs/IRE system exhibits a regulatory function in relation to the expression of ferritin, rats were fed either a control diet (C, 35 mg/kg Fe) or an iron-overloaded diet (IO, 25, 000 mg/kg Fe) for 8 weeks. In accordance with the current regulatory theory, iron overloading was found to reduce the spontaneous IRE-binding activities of hepatic IRPs. Changes in ferritin content and mitochondrial aconitase activity were consistent with the regulation of their abundance by IRPs.

並列關鍵字

iron regulatory proteins ； iron-overloading ； ferritin ； aconitase ； rats