An Integrated Approach to Evaluate Acetamiprid-induced Oxidative Damage to tRNA in Human Cells based on Oxidized Nucleotide and tRNA Profiling

Huixia Zhang; Dian Yu; Jianfeng Sun; Ling Zeng; Cai-Yun Wang; Liping Bai; Guo‐Yuan Zhu; Zhi‐Hong Jiang; Wei Zhang

Highlights

  • This study’s novelty lies in exploring the impact of acetamiprid-induced oxidative stress on RNA molecules, mainly transfer RNA (tRNA), which has not been previously investigated despite the established connection between oxidative stress and acetamiprid-induced toxicities.
  • Prior research has shown that oxidative stress can induce changes in transfer RNAs (tRNAs), such as tRNA cleavage, reprogramming of tRNA modifications, and impairment of aminoacyl-tRNA synthetase editing sites. This accumulation of evidence underscores the role of oxidative stress in altering tRNA structures and functions.
  • This study looks into the impact of acetamiprid-induced oxidative stress on RNAs, particularly tRNA. The research fills a gap in our understanding of how oxidative stress affects RNA molecules and their functions, marking a noteworthy advancement in the field.

Summary

Acetamiprid-induced oxidative stress can harm DNA and tRNA, leading to health problems. A study conducted by Huixia Zhang at Macau University of Science and Technology in 2023 introduced a comprehensive approach to assessing acetamiprid-induced oxidative damage to tRNA in human cells through oxidized nucleotide and tRNA profiling. Acetamiprid, a modern insecticide, is known for causing oxidative stress and related toxicity. Despite its impact on oxidative stress, the effects of acetamiprid-induced oxidative stress on RNA, especially tRNA, remained unexplored until this study.

Acetamiprid was found to elevate reactive oxygen species (ROS) production in HepG2 and LO2 cells, contributing to mitochondrial damage, free radical generation, and antioxidant status depletion. Oxidative damage to DNA and RNA can harm organisms, with prior research addressing RNA damage in aging, neurodegenerative diseases, and mental illnesses. However, its role in acetamiprid-induced toxicities has not been investigated.

The study employed TMSD labeling-based LC-MS/MS to measure oxidized nucleotide levels in HepG2 and LO2 cells treated with two mM acetamiprid. It also examined the impact of acetamiprid on the 8-oxo-G content of tRNAs and created volcano plots to compare RNase T1 digestion products of tRNAs from untreated and acetamiprid-treated cells.

The study’s findings align with existing knowledge, as Zhang noted, “OGG1 is an enzyme that removes 8-oxoguanine from damaged DNA and is associated with cancer cell growth. The TCGA database shows that hepatocellular carcinoma has higher levels of OGG1 compared to healthy liver tissues.”

H.-X. Zhang et al., “An integrated approach to evaluate acetamiprid-induced oxidative damage to tRNA in human cells based on oxidized nucleotide and tRNA profiling,” Environment International, vol. 178, p. 108038, Aug. 2023, doi: .

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