College of Veterinary Medicine, South China Agriculture University, Guangzhou 510642, Guangdong, PR China.
College of Veterinary Medicine, South China Agriculture University, Guangzhou 510642, Guangdong, PR China.
Ecotoxicol Environ Saf. 2021 Oct 15;223:112587. doi: 10.1016/j.ecoenv.2021.112587. Epub 2021 Aug 2.
Cu is a metallic element that widely spread over in the environment, which have raised wide concerns about the potential toxic effects and public health threat. The objective of this study aimed to investigate the impression of copper (Cu)-triggered toxicity on mitochondrial dynamic, oxidative stress, and unfolded protein response (UPR) in fundic gland of pigs. Weaned pigs were randomly distributed into three groups, fed with different Cu of 10 mg/kg (control group), 125 mg/kg (group I), and 250 mg/kg (group Ⅱ). The trial persisted for 80 days and the fundic gland tissues were collected for further researches. Moreover, the markers participated to mitochondrial dynamic, UPR，and oxidative stress in fundic gland were determined. Results revealed that vacuolar degeneration were observed in the treated groups contrast with control group, and the Cu level was boosted with the increasing intake of Cu. Besides that, the levels of CAT, TRX, HO, and GPDH were reduced in group Ⅰ and group Ⅱ, the mRNA levels of NRF2, HO-1, SOD-1, CAT, SOD-2, GSR, GPX1, GPX4, and TRX in the treated groups were promoted contrast to control group. Furthermore, the protein expression of KEAP1 was dramatically decreased, and the protein expression of NRF2, TRX and HO-1 were markedly enhanced in group Ⅰ and Ⅱ at 80 days. Moreover, the mRNA and protein expression levels of MFN1, MFN2, and OPA1 down-regulated and protein level of DRP1 was increased with the adding levels of Cu. Nevertheless, the UPR-related mRNA levels of CLPP, HTRA-2, CHOP, HSP10, and HSP60 were enhanced dramatically in Cu treatment group compared with control group. In general, our current study demonstrated that excessive absorption of Cu in fundic gland were related with stimulating UPR, oxidative stress, and the NRF2 interceded antioxidant defense. These results could afford an updated evidence on molecular theory of Cu-invited toxicity.
铜是一种广泛存在于环境中的金属元素，其潜在的毒性作用和对公众健康的威胁引起了广泛关注。本研究旨在探讨铜（Cu）引发的毒性对猪胃底腺线粒体动态、氧化应激和未折叠蛋白反应（UPR）的影响。断奶猪被随机分为三组，分别用 10mg/kg（对照组）、125mg/kg（I 组）和 250mg/kg（II 组）的铜饲养。试验持续 80 天，收集胃底腺组织进行进一步研究。此外，还测定了胃底腺中参与线粒体动态、UPR 和氧化应激的标志物。结果显示，与对照组相比，处理组出现空泡变性，且随着铜摄入量的增加，铜水平升高。此外，I 组和 II 组的 CAT、TRX、HO 和 GPDH 水平降低，NRF2、HO-1、SOD-1、CAT、SOD-2、GSR、GPX1、GPX4 和 TRX 的 mRNA 水平在处理组中升高，与对照组相比。此外，KEAP1 蛋白表达显著降低，I 组和 II 组 NRF2、TRX 和 HO-1 蛋白表达明显增强。此外，MFN1、MFN2 和 OPA1 的 mRNA 和蛋白表达水平下调，DRP1 蛋白水平升高，随着铜水平的增加。然而，与对照组相比，Cu 处理组的 UPR 相关 mRNA 水平的 CLPP、HTRA-2、CHOP、HSP10 和 HSP60 显著升高。总之，本研究表明，胃底腺中过量的铜吸收与刺激 UPR、氧化应激和 NRF2 介导的抗氧化防御有关。这些结果为铜诱导毒性的分子理论提供了新的证据。
