UBA52 Mediates ribosomal DNA stability under hexavalent chromium exposure in occupational workers and cellular models

IF 6.2 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety Pub Date : 2025-03-15 DOI:10.1016/j.ecoenv.2025.118047

Huadong Xu , Fan Wu , Chuyan Zhang , Chan Ding , Shuqian Chen , Lingfang Feng , Junfei Chen , Zhaoqiang Jiang , Yongxin Li , Jianlin Lou

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引用次数: 0

Abstract

Hexavalent chromium [Cr(VI)] exposure poses substantial environmental and health risks, especially in occupational settings, where it has been linked to genomic instability. Our previous research demonstrated that Cr(VI) exposure could induce DNA copy number (CN) variation. Here, we examined the role of Ubiquitin A-52 ribosomal protein fusion product 1 (UBA52) in stabilizing rDNA CN under Cr(VI) exposure by analyzing data from Cr(VI)-exposed workers and matched controls. Results showed significantly elevated blood Cr levels, increased γH2AX expression, and higher rDNA CN in exposed individuals, alongside upregulated UBA52 mRNA and protein levels. Spearman and regression analyses identified positive correlations between Cr levels and UBA52 expression, and between UBA52 expression and rDNA CN. In vitro studies in BEAS-2BR and HeLa cells confirmed Cr(VI)-induced upregulation of UBA52, and UBA52 knockdown led to rDNA CN instability in cells. These findings highlight that UBA52 contributes to preserving rDNA stability in the face of Cr(VI)-induced genomic stress, providing valuable insights into molecular responses to environmental Cr(VI) exposure.

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暴露于六价铬[Cr(VI)]会对环境和健康造成巨大风险，尤其是在职业环境中，它与基因组的不稳定性有关。我们之前的研究表明，接触六价铬会诱发 DNA 拷贝数（CN）变异。在此，我们通过分析接触过六价铬的工人和匹配对照组的数据，研究了泛素 A-52 核糖体蛋白融合产物 1（UBA52）在六价铬暴露下稳定 rDNA CN 的作用。结果表明，暴露个体的血铬水平明显升高，γH2AX表达增加，rDNA CN升高，同时UBA52 mRNA和蛋白质水平上调。斯皮尔曼和回归分析确定了铬水平与 UBA52 表达之间以及 UBA52 表达与 rDNA CN 之间的正相关性。在 BEAS-2BR 和 HeLa 细胞中进行的体外研究证实了 Cr(VI) 诱导的 UBA52 上调，而 UBA52 基因敲除会导致细胞中 rDNA CN 不稳定。这些发现突出表明，面对六价铬诱导的基因组应激，UBA52有助于保持rDNA的稳定性，为了解环境六价铬暴露的分子反应提供了宝贵的信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ecotoxicology and Environmental Safety 环境科学-毒理学

CiteScore

12.10

自引率

5.90%

发文量

1234

审稿时长

88 days

期刊介绍： Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.