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Transient receptor potential ankyrin 1 contributes to the ATP-elicited oxidative stress and inflammation in THP-1-derived macrophage

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Abstract

P2X7 receptor (P2X7R) is an ATP-gated non-selective cation channel which mediates ATP-induced inflammation in macrophages. Transient receptor potential (TRP) receptors are nociceptors in cellular membrane which can perceive the stimuli of environmental irritant. The interaction between TRP channels and P2X7R has been found while the details about inflammation are still unclear. In this study, we suggested that transient receptor potential ankyrin 1 (TRPA1), a member of TRP superfamily, participates in ATP-induced oxidative stress and inflammation in human acute monocytic leukemia cell line (THP-1)-derived macrophage. The co-localization between TRPA1 and P2X7R was detected using immunofluorescence in THP-1-derived macrophage and transfected human embryonic kidney cell line (HEK293T). The mechanism by which ATP or 3′-O-(4-Benzoylbenzoyl)-ATP (BzATP) induces the activation of macrophages was verified by calcium imaging, mitochondrial reactive oxygen species (mtROS) detection, mitochondrial membrane potential (∆Ψm) measurement, flow cytometry, enzyme-linked immunosorbent assay (ELISA), western blotting, CCK-8 assay, and the lactate dehydrogenase (LDH) release cytotoxic assay. The BzATP and ATP induced calcium overload, mitochondria injury, interleukin-1β (IL-1β) secretion, and cytotoxicity can be inhibited by TRPA1 antagonists. These results indicated that TRPA1 can co-localize with P2X7R and mediate ATP-induced oxidative stress and inflammation. Therefore, the inhibition of TRPA1 may provide a potential therapy for ATP-elicited inflammatory diseases, including atherosclerosis.

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Acknowledgements

This study was funded by The National Natural Science Foundation of China (31671211), Science and Technology Planning Project of Guangdong Province, China (2017B030314056), frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (2018GZR110105020) and Guangdong Provincial Natural Science Foundation (2017A030313757 and 2016A030313170). Kind gift of THP-1 cell line from Dr. Peng Li, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, China and kind gift of rat TRPA1 plasmid from Dr. Zhaobing Gao, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China, are deeply appreciated.

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Authors and Affiliations

  1. Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China

    Chao Tian, Xiaobo Han, Feng Tang, Rongqi Huang, Zuoxian Lin, Shuai Li, Hualin Huang, Huifang Zhao & Zhiyuan Li

  2. Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China

    Sihao Deng & Zhiyuan Li

  3. Guangzhou JYK Biotechnology Company Limited, Guangzhou, Guangdong, China

    Chao Tian, Feng Tang, Junjie Xu & Zhiyuan Li

  4. Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China

    Chao Tian, Xiaobo Han, Feng Tang, Rongqi Huang, Zuoxian Lin, Shuai Li, Hualin Huang, Huifang Zhao & Zhiyuan Li

  5. GZMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China

    Zhiyuan Li

  6. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Lang He

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  1. Chao Tian
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Tian, C., Han, X., He, L. et al. Transient receptor potential ankyrin 1 contributes to the ATP-elicited oxidative stress and inflammation in THP-1-derived macrophage. Mol Cell Biochem 473, 179–192 (2020). https://doi.org/10.1007/s11010-020-03818-3

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