Schümann K, Brennan K, Weiss M, Pantopoulos K, Hentze M W
Lehrstuhl für Ernährungsphysiologie der TUM, Weihenstephan, Germany.
Eur J Clin Invest. 2004 Apr;34(4):275-82. doi: 10.1111/j.1365-2362.2004.01335.x.
Iron regulatory protein 1 (IRP1), a post-transcriptional regulator of iron metabolism, is activated in the duodenum of iron-deficient animals, which is associated with increased iron absorption. In cell cultures IRP1 was also activated by iron-independent signals, such as H(2)O(2). Here we investigate whether luminal perfusion of rat duodenum with H(2)O(2) activates duodenal IRP1 and modulates duodenal iron absorption.
Duodena from iron-adequate Sprague-Dawley rats were luminally perfused with H(2)O(2). Iron regulatory protein-1 activity was determined in duodenal mucosa or in villus and crypt preparations by an electrophoretic mobility shift assay. Duodenal (59)Fe absorption was measured in isolated, perfused duodenal segments ex vivo and in ligated loops in vivo. (59)Fe uptake from the blood side was assessed after i.v. injection of (59)Fe-nitrilotriacetic acid.
Similar to iron deficiency, the perfusion with 0-50 mM of H(2)O(2) increases duodenal IRP1 activity along the entire crypt villus-axis in a dose-dependent manner. After H(2)O(2) treatment, IRP1 remains activated for 12-24 h in the tips and for 72 h in the crypts. In iron-deficiency, IRP activation correlates with increased (59)Fe absorption. However, the H(2)O(2) treatment fails to stimulate any increase in (59)Fe uptake, without promoting damage of mucosal architecture or impairing glucose and water transport.
Duodenal (59)Fe uptake is not affected by the H(2)O(2)-mediated activation of IRP1.
铁调节蛋白1（IRP1）是铁代谢的转录后调节因子，在缺铁动物的十二指肠中被激活，这与铁吸收增加有关。在细胞培养中，IRP1也可被非铁依赖性信号激活，如H₂O₂。在此，我们研究向大鼠十二指肠腔内灌注H₂O₂是否会激活十二指肠IRP1并调节十二指肠铁吸收。
用H₂O₂向铁充足的Sprague-Dawley大鼠的十二指肠腔内灌注。通过电泳迁移率变动分析测定十二指肠黏膜、绒毛和隐窝制剂中的铁调节蛋白-1活性。在离体灌注的十二指肠段和体内结扎肠袢中测量十二指肠⁵⁹Fe吸收。静脉注射⁵⁹Fe-次氮基三乙酸后评估从血液侧摄取的⁵⁹Fe。
与缺铁相似，用0-50 mM的H₂O₂灌注会以剂量依赖的方式增加整个隐窝-绒毛轴上的十二指肠IRP1活性。H₂O₂处理后，IRP1在绒毛顶端保持激活12-24小时，在隐窝中保持激活72小时。在缺铁状态下，IRP激活与⁵⁹Fe吸收增加相关。然而，H₂O₂处理未能刺激⁵⁹Fe摄取增加，且未促进黏膜结构损伤或损害葡萄糖和水的转运。
十二指肠⁵⁹Fe摄取不受H₂O₂介导的IRP1激活的影响。
