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TF-b 在鲤鱼铁稳态和细菌防御中的作用。

The role of TF-b in iron homeostasis and bacterial defense in common carp (Cyprinus carpio).

机构信息

Henan Province Engineering Research Center of Aquatic Animal Disease Control, College of Fisheries, Henan Normal University, Henan Province, PR China.

Henan Province Engineering Research Center of Aquatic Animal Disease Control, College of Fisheries, Henan Normal University, Henan Province, PR China.

出版信息

Int J Biol Macromol. 2024 Nov;280(Pt 4):136011. doi: 10.1016/j.ijbiomac.2024.136011. Epub 2024 Sep 28.

DOI:10.1016/j.ijbiomac.2024.136011
PMID:39343272
Abstract

Transferrin (TF) is a prototypical biological macromolecule protein known for its iron-binding properties. TF proteins play a crucial role in modulating host iron homeostasis and defending against pathogen invasion. In this study, we utilized common carp (Cyprinus carpio) tissues and Epithelioma papulosum cyprinid (EPC) cells to establish experimental models of iron overload with FeCl or ferric amine citrate (FAC), and to establish experimental models of bacterial infection with Aeromonas hydrophila. The current research has successfully identified the CcTF-b gene in common carp, revealing an ORF of 2001 bp with N-terminal and C-terminal structures. CcTF-b exhibited inhibitory effects on the growth of LPS and LTA in vitro. In the experimental models, the upregulations of PTGS2a and PTGS2a-like mRNA and protein levels were observed. Overexpression or interference with CcTF-b levels can modulate the expression of ferroptosis-related genes, inflammatory cytokines, lipid reactive oxygen species, GSH/GSSH levels, and Fe concentration. Significantly, the expression levels of Nrf2 and GPX4 mRNA and protein, as well as the bacterial load of A. hydrophila, could be also modulated either by upregulating or downregulating CcTF-b factors. In conclusion, in this study, these findings suggest that CcTF-b plays a critical role in the innate immune response of common carp.

摘要

转铁蛋白(TF)是一种典型的生物大分子蛋白质,以其铁结合特性而闻名。TF 蛋白在调节宿主铁平衡和抵御病原体入侵方面发挥着关键作用。在这项研究中,我们利用鲤鱼组织和鲤鱼上皮瘤细胞(EPC)建立了铁过载的实验模型(用 FeCl 或柠檬酸铁铵(FAC))和细菌感染的实验模型(用嗜水气单胞菌)。目前的研究成功地在鲤鱼中鉴定了 CcTF-b 基因,揭示了一个 2001bp 的 ORF,具有 N 端和 C 端结构。CcTF-b 在体外对 LPS 和 LTA 的生长具有抑制作用。在实验模型中,观察到 PTGS2a 和 PTGS2a 样 mRNA 和蛋白水平的上调。CcTF-b 水平的过表达或干扰可以调节铁死亡相关基因、炎症细胞因子、脂质活性氧、GSH/GSSH 水平和 Fe 浓度的表达。值得注意的是,Nrf2 和 GPX4 mRNA 和蛋白的表达水平以及 A. hydrophila 的细菌负荷也可以通过上调或下调 CcTF-b 因子来调节。总之,在这项研究中,这些发现表明 CcTF-b 在鲤鱼的固有免疫反应中发挥着关键作用。

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