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镉通过 ROS 依赖的 PTEN/PI3K/AKT 信号通路诱导猪胸腺细胞凋亡。

Cadmium induces the thymus apoptosis of pigs through ROS-dependent PTEN/PI3K/AKT signaling pathway.

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.

Quality and Safety Institute of Agricultural Products, Heilongjiang Academy of Agricultural Sciences, Harbin, 150000, China.

出版信息

Environ Sci Pollut Res Int. 2021 Aug;28(29):39982-39992. doi: 10.1007/s11356-021-13517-1. Epub 2021 Mar 25.

Abstract

Cadmium (Cd) is a transition metal that is toxic to living organisms in the environment and endangers living organisms. To explore whether Cd induces apoptosis in pig thymus and its possible mechanism, the role Cd induction of the PTEN/PI3K/Akt pathway in apoptosis of thymus cells was studied in pigs. We found that Cd exposure (the feed is treated with Cd) significantly increased Cd accumulation in the thymus of pigs. The TUNEL assay confirmed the typical apoptotic characteristics of thymus in Cd group. Moreover, in the Cd group, the activities of antioxidant indices decreased significantly, while the levels of oxidative stress indexes increased significantly, and the mRNA levels of GSH, CAT, Gpx1, GST, SOD1, and SOD2 decreased obviously. Moreover, the mRNA and protein levels of PTEN/PI3K/AKT and apoptosis-related genes were detected by qPCR and western blotting. The results show that the expressions of PI3K and AKT decreased, while the expression of PTEN increased, indicating that pathway activated. With the PTEN/PI3K/AKT pathway regulating, Bcl-2 expression decreased. Conversely, the mRNA and protein expression of apoptosis-related genes were up-regulated. In conclusion, accumulation of Cd in the pigs caused oxidative damage to immune tissues. In addition, Cd-induced oxidative stress activates the PTEN/PI3K/AKT pathway, inducing apoptosis in the thymus of pigs.

摘要

镉(Cd)是一种对环境中的生物有毒的过渡金属,会危及生物的生存。为了探索镉是否会诱导猪胸腺细胞凋亡及其可能的机制,本研究在猪中研究了镉诱导的 PTEN/PI3K/Akt 通路在胸腺细胞凋亡中的作用。我们发现,镉暴露(饲料用镉处理)显著增加了猪胸腺中的镉积累。TUNEL 检测证实了 Cd 组胸腺的典型凋亡特征。此外,在 Cd 组中,抗氧化指标的活性显著降低,而氧化应激指标的水平显著升高,GSH、CAT、Gpx1、GST、SOD1 和 SOD2 的 mRNA 水平明显降低。此外,通过 qPCR 和 Western blot 检测了 PTEN/PI3K/AKT 和凋亡相关基因的 mRNA 和蛋白水平。结果表明,PI3K 和 AKT 的表达减少,而 PTEN 的表达增加,表明通路被激活。随着 PTEN/PI3K/AKT 通路的调节,Bcl-2 的表达减少。相反,凋亡相关基因的 mRNA 和蛋白表达上调。综上所述,猪体内镉的积累导致免疫组织发生氧化损伤。此外,Cd 诱导的氧化应激激活了 PTEN/PI3K/Akt 通路,诱导了猪胸腺细胞的凋亡。

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