Zearalenone induces apoptosis in bovine mammary epithelial cells by activating endoplasmic reticulum stress.

Published on Sep 5, 2019in Journal of Dairy Science3.333
· DOI :10.3168/JDS.2018-16216
Yurong Fu4
Estimated H-index: 4
(JLU: Jilin University),
Yongcheng Jin8
Estimated H-index: 8
(JLU: Jilin University)
+ 11 AuthorsJing Zhang5
Estimated H-index: 5
(JLU: Jilin University)
Source
Abstract
ABSTRACT Zearalenone (ZEA) is a common mycotoxin produced by fungi within the genus Fusarium. However, few studies have examined the direct effects of the toxin on the mammary glands. In the present study, the effects of ZEA treatment on bovine mammary epithelial cells (MAC-T) from dairy cows were investigated. The cells were treated with different concentrations of ZEA to evaluate the effect of the toxin on cell viability, intracellular reactive oxygen species (ROS) concentrations, mitochondrial membrane potential, endoplasmic reticulum (ER) stress, and the expression of apoptosis-related genes. The results indicated that different concentrations (5, 10, 15, 20, 25, 30, 50, 60, or 100 μM) of ZEA were able to inhibit growth of MAC-T cells. After exposing the MAC-T cells to 30 μM ZEA, compared with the control group, ROS levels increased, mitochondrial membrane potential decreased, and mRNA expression of the ER-specific stress-related genes GRP78, HSP70, ATF6, EIF2A, ASK1, and CHOP was upregulated in the ZEA-treated group. Further, we analyzed the increase in apoptotic rate by flow cytometry. At the mRNA level, compared with the control group, the expression of the apoptosis-promoting gene BAX was increased in the ZEA-treated group, the expression of the inhibitory gene BCL2 decreased, and the expression of the gene CASP3 increased. We observed a significant increase in caspase-3 activity in ZEA-treated MAC-T cells. Furthermore, the apoptotic rate of the cells in the ZEA group treated with 4-phenylbutyric acid (ER stress inhibitor) decreased and the mRNA expression levels of ER stress markers GRP78 and CHOP decreased. Compared with the ZEA treatment group, the mRNA expression level of the apoptosis-related gene BAX was decreased and the expression level of BCL2 was increased in the ZEA + 4-phenylbutyric acid cotreatment group. These findings indicate that ZEA-induced ER stress increases apoptosis in MAC-T cells. The treatment of MAC-T cells with ZEA reduced cell viability, increased ROS content, decreased mitochondrial membrane potential, increased ER stress marker expression, and induced apoptosis.
📖 Papers frequently viewed together
20183.27Molecules
9 Authors (Miao Long, ..., Jianbin He)
13 Citations
2 Citations
3 Authors (Yaqiu Sang, ..., Genyi Zhang)
19 Citations
References39
Newest
#1Xin Wang (JLU: Jilin University)H-Index: 5
#2Hao Yu (JLU: Jilin University)H-Index: 8
Last. Jing Zhang (JLU: Jilin University)H-Index: 5
view all 12 authors...
ABSTRACTZearalenone (ZEA) is a mycotoxin that is mainly produced by Fusarium fungi in food and feed. It causes many adverse effects on mammals, but there is little research on the effects of ZEA on intestinal mucosal immunity and intestinal flora in animals or humans. In this study, we aimed to explore the effects of short-term ZEA exposure on mucosal immunity and the microecological balance of the intestine. We found that the morphological structure of the intestinal mucosa in mice was severely...
10 CitationsSource
#1Dacheng Yang (JNU: Jinan University)H-Index: 3
#2Xinwei Jiang (JNU: Jinan University)H-Index: 11
Last. Weibin Bai (JNU: Jinan University)H-Index: 18
view all 9 authors...
Abstract Zearalenone is commonly generated from moldy cereal grain, which is toxic to the development of gametogenesis and embryo in human and animals. The zearalenone-induced reproductive damage is mainly attributed to four mechanisms. Firstly, zearalenone as an oestrogen-like compound binds to estrogen receptor and causes damage to germ cells and testicular structure. Secondly, zearalenone disrupts the blood-testis barrier, and causes the damage to germ cells. Thirdly, zearalenone elevates oxi...
24 CitationsSource
#1Yi-Lun Lee (KMU: Kaohsiung Medical University)H-Index: 4
#1Yi-Lun Lee (KMU: Kaohsiung Medical University)H-Index: 2
Last. Yung-Shun JuanH-Index: 17
view all 8 authors...
Metabolic syndrome (MetS) and ovarian hormone deficiency could affect bladder storage dysfunction. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound in green tea, has been shown to protect against ovarian hormone deficiency induced overactive bladder (OAB). The present study investigated oxidative stress induced by MetS and bilateral ovariectomy (OVX), and elucidated the mechanism underlying the protective effect of EGCG (10 umol/kg/day) on bladder overactivity. Rats were fed with high ...
4 CitationsSource
#1Giuseppe PiccioneH-Index: 35
#2Stefania CasellaH-Index: 20
Last. Giovanni CaolaH-Index: 23
view all 5 authors...
The aim of the present work was to measure and evaluate the effect of the stage of lactation on serum homocysteine and oxidative stress in ewes. For our study ten Comisana ewes, 3 years old, clinically healthy, with the same level of production and during the same milking period were used and antioxidant barrier (Oxy-adsorbent), reactive oxygen species (dROMs), thiol antioxidant barrier (SHp) and homocysteine (sHcy) were investigated. One-way repeated measures analysis of variance (ANOVA), follo...
11 CitationsSource
#1Wanglong Zheng (YZU: Yangzhou University)H-Index: 11
#2Bingjie Wang (YZU: Yangzhou University)H-Index: 5
Last. Jianchun BianH-Index: 22
view all 14 authors...
Zearalenone (ZEA) can perturb the differentiation of cells, reduce the generation of reproductive cells and induce a death of germ cells, but the molecular mechanism remains unclear. In order to investigate the potential mechanism of ZEA-induced cell cycle arrest and apoptosis, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins, cell death, cell apoptosis, ROS generation and the ATP/AMPK pathway in Sertoli cells. The role of ROS, ER stress a...
46 CitationsSource
#1Elena Tatay (University of Valencia)H-Index: 4
#2Silvia Espín (University of Murcia)H-Index: 17
Last. María-José Ruiz (University of Valencia)H-Index: 23
view all 4 authors...
Abstract Mycotoxin contamination of foods and feeds represent a serious problem worldwide. Zearalenone (ZEA) is a secondary metabolite produced by Fusarium species. This study explores oxidative cellular damage and intracellular defense mechanisms (enzymatic and non-enzymatic) in the hepatoma cell line HepG2 after exposure to ZEA and its metabolites (α-zearalenol, α-ZOL; β-zearalenol, β-ZOL). Our results demonstrated that HepG2 cells exposed to ZEA, α-ZOL or β-ZOL at different concentrations (0,...
29 CitationsSource
#1Jian-hui Yang (Xi'an Jiaotong University)H-Index: 3
#2Qiong Wu (Xi'an Jiaotong University)H-Index: 2
Last. Hui-yong Nie (Xi'an Jiaotong University)H-Index: 2
view all 4 authors...
Apoptosis of osteoblasts triggered by high-dose glucocorticoids (GCs) has been identified as a major cause of osteoporosis. However, the molecular mechanisms underlying GC-induced osteoporosis remain elusive. This study was conducted to make clear the mechanism of GC-induced osteoblast apoptosis and to examine whether reduction of ER stress by 4-PBA inhibited osteoblast apoptosis. After treatment with dexamethasone (Dex) or hydrocortisone, cell viability was assessed using an MTT assay. Flow cyt...
12 CitationsSource
Milk and dairy products continue to raise concerns with regard to contamination with mycotoxins, most of which have a likely or confirmed carcinogenic status. Such concerns are more serious for certain cheeses due to their frequent contamination with high concentrations of mycotoxins from various sources, including the milk used as a raw material and moulds found as contaminants or purposely added for ripening. Different control measures have been suggested to prevent the formation or to remove ...
32 CitationsSource
#1Ji Hae Seo (SNU: Seoul National University)H-Index: 26
#2Ji-Hyeon Park (SNU: Seoul National University)H-Index: 9
Last. Kyu-Won Kim (SNU: Seoul National University)H-Index: 71
view all 19 authors...
The chaperone Hsp70 has a dual role, promoting both protein refolding and protein degradation. Seo and Park et al. show that Hsp70 acetylation enhances protein refolding after stress, and that subsequent deacetylation progressively promotes ubiquitin ligase binding and protein degradation.
53 CitationsSource
#1Elena Tatay (University of Valencia)H-Index: 4
#2Guillermina Font (University of Valencia)H-Index: 66
Last. María-José Ruiz (University of Valencia)H-Index: 23
view all 3 authors...
Zearalenone (ZEA) and its metabolites (α-zearalenol; α-ZOL, β-zearalenol; β-ZOL) are secondary metabolites of Fusarium fungi that produce cell injury. The present study explores mycotoxin-induced cell damage and cellular protection mechanisms in CHO-K1 cells. Cytotoxicity has been determined by reactive oxygen species (ROS) production and DNA damage. ROS production was determined using the fluorescein assay and DNA strand breakage by comet assay. Intracellular protection systems were glutathione...
32 CitationsSource
Cited By5
Newest
#1Jing Wu (HAU: Hunan Agricultural University)H-Index: 15
#2Jiayan Li (HAU: Hunan Agricultural University)
Last. Jine Yi (HAU: Hunan Agricultural University)H-Index: 12
view all 0 authors...
Abstract null null Zearalenone (ZEA) is an estrogenic toxin produced by Fusarium strains, that is widely present in crops, and endangers the reproductive system of animals. Tannic acid (TA) is a natural polyphenolic substance that is widespread in the roots, stems, and leaves of plants, and has special pharmacological activity. This study was designed to investigate the therapeutic effect of TA on ZEA-induced ovarian damage in mice and to explore the molecular mechanism involved. Ninety healthy ...
Source
#1Meimei WangH-Index: 1
#2Yan LiH-Index: 1
Last. Li JianguoH-Index: 2
view all 10 authors...
Dairy cows are susceptible to reproductive disorders, which are thought to be associated with oxidative stress. In the study, we investigated the effects of vitamin E (VE) and selenium (Se) on the proliferation, apoptosis, and steroidogenesis in bovine ovarian granulosa cells under hydrogen peroxide (H2O2) - induced oxidative stress and elaborated the underlying mechanisms. Our results showed that VE or Se could stimulate the granulosa cell proliferation, possibly due to up-regulating the expres...
Source
#1Xingde Du (Zhengzhou University)H-Index: 6
#2Haohao Liu (Zhengzhou University)H-Index: 7
Last. Huizhen Zhang (Zhengzhou University)H-Index: 10
view all 13 authors...
Abstract As an emerging pollutant in the aquatic environment, microcystin-LR (MC-LR) can enter the body through multiple pathways, and then induce apoptosis and gonadal damage, affecting reproductive function. Previous studies focused on male reproductive toxicity induced by MC-LR neglecting its effects on females. The apoptotic signal-regulated kinase 1 (ASK1) is an upstream protein of P38/JNK pathway, closely associated with apoptosis and organ damage. However, the role of ASK1 in MC-LR-induce...
Source
#1Yurong Fu (JLU: Jilin University)H-Index: 4
#2Yongcheng Jin (JLU: Jilin University)H-Index: 8
Last. Yue Tian (JLU: Jilin University)
view all 12 authors...
Zearalenone (ZEA) is a mycotoxin of the Fusarium genus that can cause endoplasmic reticulum (ER) stress and Apoptosis in bovine mammary epithelial cells (MAC-T). Polydatin (PD), a glycoside purified from Polygonum cuspidatum, has antioxidant properties. This study aimed to explore whether PD can alleviate ZEA-induced damage on bovine mammary epithelial cells (MAC-T). We found that incasing the concentration of ZEA (0, 7.5, 15, 30, 60, 90, 120, and 240 μM) gradually decreased the cell viability. ...
Source
#1Fojan Agahi (University of Valencia)H-Index: 2
#2Neda Alvarez-Ortega (University of Cartagena)H-Index: 4
Last. Cristina Juan (University of Valencia)H-Index: 25
view all 5 authors...
Abstract The co-presence of mycotoxins from fungi of the genus Fusarium is a common fact in raw food and food products, as trace levels of them or their metabolites can be detected, unless safety practices during manufacturing are carried out. Zearalenone (ZEA), its metabolites α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL) and, beauvericin (BEA) are co/present in cereals, fruits or their products which is a mixture that consumer are exposed and never evaluated in neuronal cells. In this study th...
6 CitationsSource
#1Diep-Khanh Ho Vo (Otto-von-Guericke University Magdeburg)H-Index: 4
#2Roland Hartig (Otto-von-Guericke University Magdeburg)H-Index: 28
Last. Norbert Nass (Otto-von-Guericke University Magdeburg)H-Index: 18
view all 5 authors...
The G-protein-coupled estrogen receptor (GPER) mediates rapid non-genomic effects of estrogen. Although GPER is able to induce proliferation, it is down-regulated in breast, ovarian and colorectal cancer. During cancer progression, high expression levels of GPER are favorable for patients’ survival. The GPER-specific agonist G1 leads to an inhibition of cell proliferation and an elevated level of intracellular calcium (Ca2+). The purpose of this study is to elucidate the mechanism of G1-induced ...
5 CitationsSource