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The generation of 5-N-glycolylneuraminic acid as a consequence of high levels of reactive oxygen species

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Abstract

The presence of N-glycolylneuraminic acid (Neu5Gc), a non-human sialic acid in cancer patients, is currently attributed to the consumption of red meat. Excess dietary red meat has been considered a risk factor causing chronic inflammation and for the development of cancers. However, it remains unknown whether Neu5Gc can be generated via a chemical reaction rather than via a metabolic pathway in the presence of high levels of reactive oxygen species (ROS) found in the inflammatory and tumor environments. In this study, the conversion of N-acetylneuraminic acid (Neu5Ac) to Neu5Gc has been assessed in vitro under conditions mimicking the hydroxyl radical-rich humoral environment found in inflammatory and cancerous tissues. As a result, Neu5Gc has been detected via liquid chromatography-multiple reaction monitoring mass spectrometry. Furthermore, this conversion has also been found to take place in serum biomatrix containing ROS and in cancer cell cultures with induced ROS production.

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Abbreviations

CE:

collision energy

CMAH:

N-acetylneuraminic acid hydroxylase

DCFH-DA:

2’,7’-dichlorodihydrofluorescein diacetate

DP:

declustering potential

LC-Q-TRAP MS; LC-MRM:

liquid chromatography-multiple reaction monitoring-mass spectrometry

Neu5Gc:

RE%, Relative Error

ROS:

reactive oxygen species

SA:

sialic acid

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Acknowledgements

The authors thank Dr. Ying Xu and Dr. Xingze Qu (The Third Hospital, Jilin University) for the discussion of Fenton reaction. The authors thank Prof. Bo Wang (Department of Chemistry, Jilin University) for the discussion of the mechanism of hydroxylation reaction.

Funding

Y.G. thanks the Department of Science and Technology of Jilin Province, China [grant number 20200801066GH].

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Author notes

  1. Ruifeng Bai and Jingyi Wang authors contributed equally.

Authors and Affiliations

  1. Key laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, China

    Ruifeng Bai, Jingyi Wang & Yin Gao

  2. Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada

    Inka Brockhausen

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  1. Ruifeng Bai
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Contributions

Y.G. conceived and designed the experiments; R.B. and J.W. performed the experiments; Y.G., R.B. and J.W. analyzed the data; Y.G., R.B., J.W. and IB contributed to the preparation of the manuscript. All authors reviewed the manuscript.

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Correspondence to Yin Gao.

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Bai, R., Wang, J., Brockhausen, I. et al. The generation of 5-N-glycolylneuraminic acid as a consequence of high levels of reactive oxygen species. Glycoconj J 40, 435–448 (2023). https://doi.org/10.1007/s10719-023-10121-y

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