Collagen Peptides as a Hypoxia-Inducible Factor-2α-Stabilizing Prolyl Hydroxylase Inhibitor to Stimulate Intestinal Iron Absorption by Upregulating Iron Transport Proteins,Journal of Agricultural and Food Chemistry

当前位置： X-MOL 学术 › J. Agric. Food Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Collagen Peptides as a Hypoxia-Inducible Factor-2α-Stabilizing Prolyl Hydroxylase Inhibitor to Stimulate Intestinal Iron Absorption by Upregulating Iron Transport Proteins
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-11-22 , DOI: 10.1021/acs.jafc.2c05411
Suqin Zhu _{1,

2} , Lingyu Wu ₂ , Meichao Zhang ₃ , Shiyang Li ₂ , Wenshuo Xing ₂ , Zifang Zhao ₄ , Hongxing Guo ₄ , Lei Ma ₂ , Haohao Wu _{2,

4}

Affiliation

Iron intervention is not always safe and effective to correct iron deficiency. Host iron absorption stimulation is emerging as a promising adjunctive/alternative treatment. Here, porcine collagen hydrolysate (CH) and collagen-derived dipeptide prolyl-hydroxyproline, rather than collagen amino acids, namely, glycine, proline, and hydroxyproline, were found to increase cellular iron reduction, absorption, and transportation, to upregulate duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferroportin (FPN), and hephaestin, and to nongenomically activate hypoxia-inducible factor-2α signaling in polarized Caco-2 cells. Prolyl-hydroxyproline showed both competitive and uncompetitive inhibition of recombinant human prolyl hydroxylase-3 activity with EC₅₀ and K_i values of 10.62 and 6.73 μM, respectively. Docking simulations revealed collagen peptides as iron chelators and/or steric hindrances for prolyl hydroxylase-3. CH and prolyl-hydroxyproline acutely increased duodenal hypoxia-inducible factor-2α stability and Dcytb, DMT1, FPN, and hephaestin transcription in rats. Overall, collagen peptides act as a hypoxia-inducible factor-2α-stabilizing prolyl hydroxylase inhibitor to stimulate intestinal iron absorption.

中文翻译：

胶原蛋白肽作为缺氧诱导因子-2α-稳定脯氨酰羟化酶抑制剂通过上调铁转运蛋白刺激肠道铁吸收

铁剂干预对于纠正铁缺乏症并不总是安全有效的。宿主铁吸收刺激正在成为一种有前途的辅助/替代治疗。在这里，猪胶原蛋白水解物 (CH) 和胶原蛋白衍生的二肽脯氨酰-羟脯氨酸，而不是胶原蛋白氨基酸，即甘氨酸、脯氨酸和羟脯氨酸，被发现可以增加细胞铁的还原、吸收和转运，从而上调十二指肠细胞色素 b (Dcytb)、二价金属转运蛋白 1 (DMT1)、铁转运蛋白 (FPN) 和 hephaestin，以及非基因组激活极化 Caco-2 细胞中的缺氧诱导因子-2α 信号传导。脯氨酰羟脯氨酸显示出对重组人脯氨酰羟化酶 3 活性的竞争性和非竞争性抑制作用，EC ₅₀和K _i值分别为 10.62 和 6.73 μM。对接模拟显示胶原蛋白肽作为铁螯合剂和/或脯氨酰羟化酶 3 的空间位阻。CH 和脯氨酰羟脯氨酸可显着增加大鼠十二指肠缺氧诱导因子 2α 的稳定性和 Dcytb、DMT1、FPN 和 hephaestin 的转录。总体而言，胶原蛋白肽可作为缺氧诱导因子 2α 稳定脯氨酰羟化酶抑制剂，刺激肠道铁吸收。

更新日期：2022-11-22

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11