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Involvement of LARP7 in Activation of SIRT1 to Inhibit NF-κB Signaling Protects Microglia from Acrylamide-Induced Neuroinflammation

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Abstract

Acrylamide (AM) is a potent neurotoxin and carcinogen that is mainly formed by the Maillard reaction of asparagine with starch at high temperatures. However, the toxicity mechanism underlying AM has not been investigated from a proteomic perspective, and the regulation of protein expression by AM remains poorly understood. This research was the first to utilize proteomics to explore the mechanism of AM exposure-induced neuroinflammation. Target proteins were obtained by differential protein analysis, functional annotation, and enrichment analysis of proteomics. Then, molecular biology methods, including Western blot, qPCR, and immunofluorescence, were used to verify the results and explore possible mechanisms. We identified 100 key differential metabolites by proteomic analysis, which was involved in the occurrence of various biological functions. Among them, the KEGG pathway enrichment analysis showed that the differential proteins were enriched in the P53 pathway, sulfur metabolism pathway, and ferroptosis. Finally, the differential target protein we locked was LARP7. Molecular biological verification found that AM exposure inhibited the expression of LARP7 and induced the burst of inflammation, while SRT1720 agonist treatment showed no effect on LARP7, but significant changes in inflammatory factors and NF-κB. Taken together, these findings suggested that AM may activate NF-κB to induce neuroinflammation by inhibiting the LARP7-SIRT1 pathway. And our study provided a direction for AM-induced neurotoxicity through proteomics and multiple biological analysis methods.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This work was supported by the National Natural Science Foundation of China (no. 81602846), the Natural Science Foundation of Shandong Province (no. ZR2021MH145 and no. ZR2022QH164), the Taishan Scholar Project of Shandong Province (no. tsqn201812159), the Key Research and Development Program of Jining Science and Technology(no.2022YXNS148), the Doctoral Fund of Jining NO.1 People’ s Hospital (no. 2021-BS-008), and the Projects of medical and health technology development program in Shandong province (no. 202113050502).

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Authors and Affiliations

  1. Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Shandong First Medical University, Jining, 272000, China

    Jinxiu Guo, Haitao Zhong, Wenxue Sun, Shiyuan Zhao, Junjun Meng & Pei Jiang

  2. Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, 272000, China

    Jinxiu Guo, Haitao Zhong, Wenxue Sun, Shiyuan Zhao, Junjun Meng & Pei Jiang

  3. Faculty of Science and Engineering, University of Nottingham Ningbo China, Ningbo, 315100, China

    Hongjia Xue

  4. Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, China

    Wenxue Sun

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  1. Jinxiu Guo
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  2. Hongjia Xue
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  3. Haitao Zhong
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Contributions

Material preparation, data collection, and analysis were performed by Jinxiu Guo, Hongjia Xue, Wenxue Sun, Shiyuan Zhao, and Junjun Meng. The first draft of the manuscript was written by Jinxiu Guo. Haitao Zhong, and Pei Jiang supervised the study.

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Correspondence to Haitao Zhong or Pei Jiang.

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Guo, J., Xue, H., Zhong, H. et al. Involvement of LARP7 in Activation of SIRT1 to Inhibit NF-κB Signaling Protects Microglia from Acrylamide-Induced Neuroinflammation. Neurotox Res 40, 2016–2026 (2022). https://doi.org/10.1007/s12640-022-00624-1

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  • DOI: https://doi.org/10.1007/s12640-022-00624-1

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