Curcumin inhibits zearalenone-induced apoptosis and oxidative stress in Leydig cells via modulation of the PTEN/Nrf2/Bip signaling pathway

Si Chen; Shuhua Yang; Mingyang Wang; Jia Chen; Sheng Huang; Zhen Wei; Ziyang Cheng; Hanli Wang; Miao Long; Peng Li

doi:10.1016/j.fct.2020.111385

Curcumin inhibits zearalenone-induced apoptosis and oxidative stress in Leydig cells via modulation of the PTEN/Nrf2/Bip signaling pathway

Food Chem Toxicol. 2020 Jul:141:111385. doi: 10.1016/j.fct.2020.111385. Epub 2020 Apr 26.

Authors

Si Chen¹, Shuhua Yang², Mingyang Wang³, Jia Chen⁴, Sheng Huang⁵, Zhen Wei⁶, Ziyang Cheng⁷, Hanli Wang⁸, Miao Long⁹, Peng Li¹⁰

Affiliations

¹ Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China. Electronic address: 2017220528@stu.syau.edu.cn.
² Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China. Electronic address: yangshuhua0001@syau.edu.cn.
³ Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China. Electronic address: m13940546231@163.com.
⁴ Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China. Electronic address: 2017220532@syau.edu.cn.
⁵ Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China. Electronic address: 2017220530@syau.edu.cn.
⁶ Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China. Electronic address: 2019250164@stu.syau.edu.cn.
⁷ Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China. Electronic address: 2019240368@stu.syau.edu.cn.
⁸ Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China.
⁹ Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China. Electronic address: longmiao@syau.edu.cn.
¹⁰ Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China. Electronic address: lipeng2018@syau.edu.cn.

PMID: 32348814
DOI: 10.1016/j.fct.2020.111385

Abstract

The toxic effect of zearalenone (ZEA) is not fully understood and there is an urgent need for the development of effective agents to protect against the toxic effects of ZEA. In this study, we detected whether curcumin (CUR) can reduce Leydig cells apoptosis induced by ZEA. The Effects of ZEA and CUR on cell viability was evaluated using a Cell Counting kit-8 assay (CCK-8). Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry. The protective effect of CUR on oxidative stress induced by ZEA was determined by ROS, MDA, T-SOD, GSH and GSH-Px levels. In addition, we also determined effects of key signaling pathways and proteins involved in the apoptotic, PI3K-AKT, Nrf2 and endoplasmic reticulum stress signaling pathways by Western blotting. The expressions of proteins (PTEN, AKT, p-AKT, Bax, Bcl-2, GRP78, CHOP, JNK, P-JNK, Caspase-12, Caspase-9, Caspase-3, Nrf2, Keap1 and HO-1) were measured. The experimental results showed that CUR can alleviate oxidative stress and apoptosis caused by ZEA through the PI3K-AKT, Nrf2 and endoplasmic reticulum stress signaling pathways. Our results provide a theoretical basis for molecular studies of ZEA toxicology and clinical application of CUR.

Keywords: Curcumin; Endoplasmic reticulum stress; Leydig cell; Nrf2 signaling pathway; PI3K-AKT signaling Pathway; Zearalenone.

MeSH terms

Animals
Cell Line
Curcumin / pharmacology*
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins / metabolism*
Leydig Cells / drug effects*
Leydig Cells / metabolism
Male
Mice
NF-E2-Related Factor 2 / metabolism*
Oxidative Stress / drug effects*
PTEN Phosphohydrolase / metabolism*
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects*
Zearalenone / toxicity*

Substances

Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Hspa5 protein, mouse
NF-E2-Related Factor 2
Nfe2l2 protein, mouse
Reactive Oxygen Species
Zearalenone
PTEN Phosphohydrolase
Pten protein, mouse
Curcumin