基于内质网应激，玉米赤霉烯酮诱导仔猪睾丸支持细胞中线粒体相关内质网膜功能障碍。

Zearalenone induces mitochondria-associated endoplasmic reticulum membranes dysfunction in piglet Sertoli cells based on endoplasmic reticulum stress.

机构信息

College of Animal Science and Technology, Anhui Agricultural University, 130 West Changjiang Road, Hefei 230036, China.

College of Animal Science and Technology, Anhui Agricultural University, 130 West Changjiang Road, Hefei 230036, China; Department of Food Science and Engineering, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China; Key Laboratory of Animal Parasitology of Ministry of Agriculture, Laboratory of Quality and Safety Risk Assessment for Animal Products on Biohazards (Shanghai) of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.

出版信息

Ecotoxicol Environ Saf. 2023 Apr 1;254:114710. doi: 10.1016/j.ecoenv.2023.114710. Epub 2023 Mar 2.

DOI:10.1016/j.ecoenv.2023.114710

PMID:36950988

Abstract

Zearalenone (ZEA) is an estrogen-like mycotoxin, which mainly led to reproductive toxicity. The study aimed to investigate the molecular mechanism of ZEA-induced dysfunction of mitochondria-associated endoplasmic reticulum membranes (MAM) in piglet Sertoli cells (SCs) via the endoplasmic reticulum stress (ERS) pathway. In this study, SCs were used as a research object that was exposed to ZEA, and ERS inhibitor 4-Phenylbutyrate acid (4-PBA) was used as a reference. The results showed that ZEA damaged cell viability and increased Ca levels; damaged the structure of MAM; up-regulated the relative mRNA and protein expression of glucose-regulated protein 75 (Grp75) and mitochondrial Rho-GTPase 1 (Miro1), while inositol 1,4,5-trisphosphate receptor (IP3R), voltage-dependent anion channel 1 (VDAC1), mitofusin2 (Mfn2) and phosphofurin acidic cluster protein 2 (PACS2) were down-regulated. After a 3 h 4-PBA-pretreatment, ZEA was added for mixed culture. The results of 4-PBA pretreatment showed that inhibition of ERS reduced the cytotoxicity of ZEA against piglet SCs. Compared with the ZEA group, inhibition of ERS increased cell viability and decreased Ca levels; restored the structural damage of MAM; down-regulated the relative mRNA and protein expression of Grp75 and Miro1; and up-regulated the relative mRNA and protein expression of IP3R, VDAC1, Mfn2, and PACS2. In conclusion, ZEA can induce MAM dysfunction in piglet SCs via the ERS pathway, whereas ER can regulate mitochondria through MAM.

摘要

玉米赤霉烯酮（ZEA）是一种类雌激素霉菌毒素，主要导致生殖毒性。本研究旨在通过内质网应激（ERS）途径研究 ZEA 诱导仔猪睾丸支持细胞（SCs）中线粒体相关内质网膜（MAM）功能障碍的分子机制。本研究以 SCs 为研究对象，用 ZEA 进行处理，并以 ERS 抑制剂 4-苯丁酸（4-PBA）作为对照。结果表明，ZEA 损害细胞活力并增加 Ca 水平；破坏 MAM 的结构；上调葡萄糖调节蛋白 75（Grp75）和线粒体 Rho-GTPase 1（Miro1）的相对 mRNA 和蛋白表达，而肌醇 1,4,5-三磷酸受体（IP3R）、电压依赖性阴离子通道 1（VDAC1）、融合蛋白 2（Mfn2）和磷酸化酸性簇蛋白 2（PACS2）的相对 mRNA 和蛋白表达下调。用 4-PBA 预处理 3 h 后，加入 ZEA 进行混合培养。4-PBA 预处理结果表明，ERS 抑制可降低 ZEA 对仔猪 SCs 的细胞毒性。与 ZEA 组相比，ERS 抑制可增加细胞活力，降低 Ca 水平；修复 MAM 的结构损伤；下调 Grp75 和 Miro1 的相对 mRNA 和蛋白表达；上调 IP3R、VDAC1、Mfn2 和 PACS2 的相对 mRNA 和蛋白表达。总之，ZEA 可通过 ERS 途径诱导仔猪 SCs 中的 MAM 功能障碍，而内质网可通过 MAM 调节线粒体。