The link between deacetylation and hepatotoxicity induced by exposure to hexavalent chromium,Journal of Advanced Research

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The link between deacetylation and hepatotoxicity induced by exposure to hexavalent chromium
Journal of Advanced Research ( IF 11.4 ) Pub Date : 2021-04-08 , DOI: 10.1016/j.jare.2021.04.002
Qingyue Yang _{1,

2} , Bing Han ₁ , Siyu Li ₁ , Xiaoqiao Wang ₁ , Pengfei Wu ₁ , Yan Liu ₁ , Jiayi Li ₁ , Biqi Han ₁ , Ning Deng ₁ , Zhigang Zhang _{1,

2}

Affiliation

Introduction

Hexavalent chromium (Cr(VI)), one of the toxic heavy metals, poses a serious threat to human and animal health. Protein acetylation regulates the structure and function of most proteins in a variety of ways. However, the hepatotoxicity of Cr(VI) and whether it is related to deacetylation remains largely unknown.

Objectives

We aimed to explore the link between the deacetylation of silent information regulator two ortholog 1 (Sirt1) and hepatotoxicity induced by Cr(VI) exposure, and to better clarify the biological mechanism of liver injury induced by Cr(VI).

Methods

We established a model of liver injury of K₂Cr₂O₇ by injecting rats intraperitoneally for 35 days continuously and adding resveratrol (Res) to further explore the link between deacetylation and hepatotoxicity.

Results

The results revealed that Cr(VI) induced inflammatory response and apoptosis in hepatocytes. Furthermore, Cr(VI) reduced Sirt1 expression and inhibited the deacetylation of Sirt1 to downstream key transcription factors, including nuclear factor erythroid 2-related factor 2 (Nrf2), Forkhead box O3 (FOXO3), and nuclear factor-kappa B (NF-κB). Conversely, when Res was administered as an activator of Sirt1, the deacetylation of Sirt1 was enhanced, and inflammatory response and apoptosis were significantly alleviated.

Conclusion

In summary, this work firstly demonstrates that Cr(VI) induces liver injury in rat by inhibiting the deacetylation of Sirt1, which is of positive significance for protecting the natural environment and animal health from chronic Cr poisoning.

中文翻译：

暴露于六价铬引起的脱乙酰化和肝毒性之间的联系

介绍

六价铬 (Cr(VI)) 是一种有毒重金属，对人类和动物的健康构成严重威胁。蛋白质乙酰化以多种方式调节大多数蛋白质的结构和功能。然而，Cr(VI) 的肝毒性以及它是否与脱乙酰化有关仍然很大程度上未知。

目标

我们旨在探索沉默信息调节因子2 ortholog 1 (Sirt1) 的去乙酰化与Cr(VI) 暴露诱导的肝毒性之间的联系，并更好地阐明Cr(VI) 诱导的肝损伤的生物学机制。

方法

我们建立了K ₂ Cr ₂ O ₇肝损伤模型，通过连续35天腹腔注射大鼠并添加白藜芦醇（Res）进一步探索去乙酰化与肝毒性之间的联系。

结果

结果表明，Cr(VI) 在肝细胞中诱导炎症反应和凋亡。此外，Cr(VI) 降低了 Sirt1 的表达并抑制了 Sirt1 对下游关键转录因子的去乙酰化，包括核因子红细胞 2 相关因子 2 (Nrf2)、叉头盒 O3 (FOXO3) 和核因子-kappa B (NF- κB)。相反，当 Res 作为 Sirt1 的激活剂给药时，Sirt1 的去乙酰化增强，炎症反应和细胞凋亡明显减轻。