Bovine lactoferrin regulates cell survival, apoptosis and inflammation in intestinal epithelial cells and preterm pig intestine

被引:54
作者
Nguyen, Duc Ninh [1 ,2 ]
Jiang, Pingping [1 ]
Stensballe, Allan [3 ]
Bendixen, Ernoke [4 ]
Sangild, Per T. [1 ]
Chatterton, Dereck E. W. [1 ,2 ]
机构
[1] Univ Copenhagen, Dept Vet Clin & Anim Sci, Comparat Pediat & Nutr, DK-1958 Copenhagen, Denmark
[2] Univ Copenhagen, Dept Food Sci, Rolighedsvej 30, DK-1958 Frederiksberg, Denmark
[3] Aalborg Univ, Dept Hlth Sci & Technol, DK-9220 Aalborg, Denmark
[4] Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark
关键词
Apoptosis; Inflammation; Lactoferrin; Necrotizing enterocolitis; MITOCHONDRIAL PERMEABILITY TRANSITION; KAPPA-B; PROLIFERATION; CANCER; FERRITIN; HIF-1; MILK; IRON;
D O I
10.1016/j.jprot.2016.03.020
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Bovine lactoferrin (bLF) may modulate neonatal intestinal inflammation. Previous studies in intestinal epithelial cells (IECs) indicated that moderate bLF doses enhance proliferation whereas high doses trigger inflammation. To further elucidate cellular mechanisms, we profiled the porcine IEC proteome after stimulation with bLF at 0, 0.1,1 and 10 g/L by LC-MS-based proteomics. Key pathways were analyzed in the intestine of formula-fed preterm pigs with and without supplementation of 10 g/L bLF. Levels of 123 IEC proteins were altered by bLF. Low bLF doses (0.1-1 g/L) up-regulated 11 proteins associated with glycolysis, energy metabolism and protein synthesis, indicating support of cell survival. In contrast, a high bLF dose (10 g/L) up-regulated three apoptosis-inducing proteins, down-regulated five anti-apoptotic and proliferation-inducing proteins and 15 proteins related to energy and amino acid metabolism, and altered three proteins enhancing the hypoxia inducible factor-1 (HIF-1) pathway. In the preterm pig intestine, bLF at 10 g/L decreased villus height/crypt depth ratio and up-regulated the Bax/Bcl-2 ratio and HIF-1 alpha, indicating elevated intestinal apoptosis and inflammation. In conclusion, bLF dose dependently affects IECs via metabolic, apoptotic and inflammatory pathways. It is important to select an appropriate dose when feeding neonates with bLF to avoid detrimental effects exerted by excessive doses. Biological significance: The present work elucidates dose-dependent effects of bLF on the proteomic changes of IECs in vitro supplemented with data from a preterm pig study confirming detrimental effects of enteral feeding with the highest dose of bLF (10 g/L). The study contributes to further understanding on mechanisms that bLF, as an important milk protein, can regulate the homeostasis of the immature intestine. Results from this study urge neonatologists to carefully consider the dose of bLF to supplement into infant formula used for preterm neonates. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:95 / 102
页数:8
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