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姜黄素通过调节 PTEN/Nrf2/Bip 信号通路抑制玉米赤霉烯酮诱导的睾丸间质细胞凋亡和氧化应激。

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

机构信息

Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China.

Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China.

出版信息

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

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

摘要

玉米赤霉烯酮(ZEA)的毒性作用尚未完全阐明,因此迫切需要开发有效的药物来预防 ZEA 的毒性作用。在本研究中,我们检测了姜黄素(CUR)是否可以减少 ZEA 诱导的睾丸间质细胞凋亡。使用细胞计数试剂盒-8(CCK-8)测定 ZEA 和 CUR 对细胞活力的影响。通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记(TUNEL)测定和流式细胞术检测细胞凋亡。通过 ROS、MDA、T-SOD、GSH 和 GSH-Px 水平测定 CUR 对 ZEA 诱导的氧化应激的保护作用。此外,我们还通过 Western blot 测定了参与凋亡的关键信号通路和蛋白质(PI3K-AKT、Nrf2 和内质网应激信号通路)的表达。测定蛋白质(PTEN、AKT、p-AKT、Bax、Bcl-2、GRP78、CHOP、JNK、P-JNK、Caspase-12、Caspase-9、Caspase-3、Nrf2、Keap1 和 HO-1)的表达。实验结果表明,CUR 可以通过 PI3K-AKT、Nrf2 和内质网应激信号通路缓解 ZEA 引起的氧化应激和细胞凋亡。我们的研究结果为 ZEA 毒理学的分子研究和 CUR 的临床应用提供了理论依据。

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