Mattace Raso Giuseppina, Irace Carlo, Esposito Emanuela, Maffettone Carmen, Iacono Anna, Di Pascale Antonio, Santamaria Rita, Colonna Alfredo, Meli Rosaria
Dipartimento di Farmacologia Sperimentale, Università degli Studi di Napoli Federico II, via D. Montesano, 49-80131 Naples, Italy.
Biochem Pharmacol. 2009 Oct 15;78(8):1001-7. doi: 10.1016/j.bcp.2009.05.034. Epub 2009 Jun 6.
Iron is essential for many biological processes and its deficiency or excess is involved in pathological conditions. At cellular level, the maintenance of iron homeostasis is largely accomplished by the transferrin receptor (TfR-1) and by ferritin, whose expression is mainly regulated post-transcriptionally by iron regulatory proteins (IRPs). This study examines the hypothesis that modification of serum estrogen levels by ovariectomy and 17beta-estradiol (E(2)) treatment in rats modulate serum iron-status parameters and iron metabolism in adipose tissue. In particular, we evaluated the RNA binding of IRP1 by electrophoretic mobility-shift assay and IRP1, ferritin, and TfR-1 expression in adipose tissue by Western blot analysis. Ovariectomy, besides a lowered serum iron and transferrin iron binding capacity, remarkably decreased the binding activity of IRP1 in peritoneal and subcutaneous adipose tissues, and these effects were reversed by E(2) treatment. Moreover, ovariectomy determined a decrease of IRP1 expression, which was significant in subcutaneous adipose tissue. Consistent with IRP1 regulation, an increase of ferritin and a decrease of TfR-1 expression were observed in peritoneal adipose tissue from ovariectomized animals, while the treatment with E(2) reconstituted TfR-1 level. A similar expression profile of TfR-1 was observed in subcutaneous adipose tissue, where ferritin level did not change in ovariectomized animals, and was increased after E(2) treatment. Our results indicate that estrogen level changes can regulate the binding activity of the IRP1, and consequently ferritin and TfR-1 expression in adipose tissue, suggesting a relationship among serum and tissue iron parameters, estrogen status and adiposity.
铁对许多生物过程至关重要,其缺乏或过量都与病理状况有关。在细胞水平上,铁稳态的维持主要通过转铁蛋白受体(TfR-1)和铁蛋白来完成,它们的表达主要在转录后由铁调节蛋白(IRPs)调控。本研究检验了这样一个假说:大鼠卵巢切除术和17β-雌二醇(E₂)处理对血清雌激素水平的改变会调节血清铁状态参数以及脂肪组织中的铁代谢。具体而言,我们通过电泳迁移率变动分析评估了IRP1的RNA结合情况,并通过蛋白质印迹分析评估了脂肪组织中IRP1、铁蛋白和TfR-1的表达。卵巢切除术除了降低血清铁和转铁蛋白铁结合能力外,还显著降低了腹膜和皮下脂肪组织中IRP1的结合活性,而E₂处理可逆转这些效应。此外,卵巢切除术导致IRP1表达下降,这在皮下脂肪组织中具有显著性。与IRP1的调控一致,在去卵巢动物的腹膜脂肪组织中观察到铁蛋白增加和TfR-1表达减少,而E₂处理可使TfR-1水平恢复。在皮下脂肪组织中观察到类似的TfR-1表达谱,去卵巢动物的铁蛋白水平未发生变化,而E₂处理后铁蛋白水平升高。我们的结果表明,雌激素水平变化可调节IRP1的结合活性,进而调节脂肪组织中铁蛋白和TfR-1的表达,提示血清和组织铁参数、雌激素状态与肥胖之间存在关联。