Human Milk Fortification Increases Bnip3 Expression Associated With Intestinal Cell Death In Vitro

作     者：Diehl-Jones, William Archibald, Alyssa Gordon, Joseph W. Mughal, Wajihah Hossain, Zakir Friel, James K. 

作者机构：Athabasca Univ Fac Hlth Disciplines Athabasca AB Canada Univ Manitoba Dept Biol Sci Winnipeg MB Canada Univ Manitoba Dept Human Anat & Cell Sci Winnipeg MB Canada Univ Manitoba Fac Nursing Winnipeg MB Canada Univ Manitoba Dept Human Nutr Sci Winnipeg MB Canada 

出 版 物：《JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION》 (儿科胃肠病学与营养杂志)

年 卷 期：2015年第61卷第5期

页      面：583-590页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 100202[医学-儿科学] 10[医学] 

基　　金：Manitoba Institute for Child Health 

主　　题：Bnip3 breast milk cell death human milk fortifier intestinal cells 

摘      要：Objectives: The aim of the present study was to determine the in vitro effect(s) of a bovine-based human breast milk fortifier (HMF) on human intestinal cells. HMF increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein (Bnip3) and cell death;the prostaglandin analogue misoprostol will rescue this effect. Methods: Cultured intestinal cells were exposed to in vitro-digested human breast milk (BM) + HMF. Intracellular oxidation, cell damage/cell death, and BNIP3 expression were measured after exposure. Results: In vitro-digested BM+ HMF significantly increased intracellular oxidation, cell damage, and cell death in enterocyte cell cultures compared with either saline or BM controls, an effect that was rescued by the prostaglandin analogue, misoprostol. Bnip3 transcript and Bnip3 protein levels were significantly increased in vitro after treatment with BM_HMF. We also provide evidence that transfection of enterocytes with Bnip3 increases cell death, an effect that is rescued by a nonfunctional Bnip3 splice variant. Conclusions: Our data support the hypothesis that HMF increases intestinal Bnip3 in vitro, and that the gene product triggers cell death. We suggest that misoprostol is a promising therapy, which may reduce intestinal cell death.