Lactoferrin Alleviated AFM1-Induced Apoptosis in Intestinal NCM 460 Cells through the Autophagy Pathway

Aflatoxin M1 (AFM1) is the only mycotoxin with maximum residue limit in milk, which may result in serious human diseases. On the contrary, lactoferrin (Lf) is an active protein with multiple functions. Studies have confirmed that Lf has a powerful potential to protect the intestines, but the influen...

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Main Authors: Hongya Wu, Yanan Gao, Songli Li, Xiaoyu Bao, Jiaqi Wang, Nan Zheng
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Foods
Subjects:
Online Access:https://www.mdpi.com/2304-8158/11/1/23
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author Hongya Wu
Yanan Gao
Songli Li
Xiaoyu Bao
Jiaqi Wang
Nan Zheng
author_facet Hongya Wu
Yanan Gao
Songli Li
Xiaoyu Bao
Jiaqi Wang
Nan Zheng
author_sort Hongya Wu
collection DOAJ
description Aflatoxin M1 (AFM1) is the only mycotoxin with maximum residue limit in milk, which may result in serious human diseases. On the contrary, lactoferrin (Lf) is an active protein with multiple functions. Studies have confirmed that Lf has a powerful potential to protect the intestines, but the influence of Lf on mycotoxins is not clear. This study aims to explore whether Lf can protect the cytotoxicity induced by AFM1, and determine the underlying mechanisms in human normal colonic epithelial NCM460 cells. The results indicated that AFM1 decreased the cell viability, and increased the levels of apoptosis and autophagy of NCM460 cells. Lf can alleviate the cytotoxicity induced by AFM1 through enhancing cell viability, significantly down-regulated the expression of apoptotic genes and proteins (<i>BAX</i>, <i>caspase3</i>, <i>caspase9</i>, caspase3, and caspase9), and regulated the gene and protein expression of autophagy factors (<i>Atg5</i>, <i>Atg7</i>, <i>Atg12</i>, <i>Beclin1</i>, <i>ULK1</i>, <i>ULK2</i>, LC3, and p62). Furthermore, interference of the key gene Atg5 of autophagy can reduce AFM1-induced apoptosis, which is consistent with the role of Lf, implying that Lf may protect AFM1-induced intestinal injury by inhibiting excessive autophagy-mediated apoptosis. Taken together, our data indicated that Lf has a mitigating effect on apoptosis induced by AFM1 through the autophagy pathway.
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spelling doaj.art-4c409d7f807b4964887236edd8a2f1502023-11-23T11:30:18ZengMDPI AGFoods2304-81582021-12-011112310.3390/foods11010023Lactoferrin Alleviated AFM1-Induced Apoptosis in Intestinal NCM 460 Cells through the Autophagy PathwayHongya Wu0Yanan Gao1Songli Li2Xiaoyu Bao3Jiaqi Wang4Nan Zheng5Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaAflatoxin M1 (AFM1) is the only mycotoxin with maximum residue limit in milk, which may result in serious human diseases. On the contrary, lactoferrin (Lf) is an active protein with multiple functions. Studies have confirmed that Lf has a powerful potential to protect the intestines, but the influence of Lf on mycotoxins is not clear. This study aims to explore whether Lf can protect the cytotoxicity induced by AFM1, and determine the underlying mechanisms in human normal colonic epithelial NCM460 cells. The results indicated that AFM1 decreased the cell viability, and increased the levels of apoptosis and autophagy of NCM460 cells. Lf can alleviate the cytotoxicity induced by AFM1 through enhancing cell viability, significantly down-regulated the expression of apoptotic genes and proteins (<i>BAX</i>, <i>caspase3</i>, <i>caspase9</i>, caspase3, and caspase9), and regulated the gene and protein expression of autophagy factors (<i>Atg5</i>, <i>Atg7</i>, <i>Atg12</i>, <i>Beclin1</i>, <i>ULK1</i>, <i>ULK2</i>, LC3, and p62). Furthermore, interference of the key gene Atg5 of autophagy can reduce AFM1-induced apoptosis, which is consistent with the role of Lf, implying that Lf may protect AFM1-induced intestinal injury by inhibiting excessive autophagy-mediated apoptosis. Taken together, our data indicated that Lf has a mitigating effect on apoptosis induced by AFM1 through the autophagy pathway.https://www.mdpi.com/2304-8158/11/1/23lactoferrinaflatoxin M1apoptosisautophagy
spellingShingle Hongya Wu
Yanan Gao
Songli Li
Xiaoyu Bao
Jiaqi Wang
Nan Zheng
Lactoferrin Alleviated AFM1-Induced Apoptosis in Intestinal NCM 460 Cells through the Autophagy Pathway
Foods
lactoferrin
aflatoxin M1
apoptosis
autophagy
title Lactoferrin Alleviated AFM1-Induced Apoptosis in Intestinal NCM 460 Cells through the Autophagy Pathway
title_full Lactoferrin Alleviated AFM1-Induced Apoptosis in Intestinal NCM 460 Cells through the Autophagy Pathway
title_fullStr Lactoferrin Alleviated AFM1-Induced Apoptosis in Intestinal NCM 460 Cells through the Autophagy Pathway
title_full_unstemmed Lactoferrin Alleviated AFM1-Induced Apoptosis in Intestinal NCM 460 Cells through the Autophagy Pathway
title_short Lactoferrin Alleviated AFM1-Induced Apoptosis in Intestinal NCM 460 Cells through the Autophagy Pathway
title_sort lactoferrin alleviated afm1 induced apoptosis in intestinal ncm 460 cells through the autophagy pathway
topic lactoferrin
aflatoxin M1
apoptosis
autophagy
url https://www.mdpi.com/2304-8158/11/1/23
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