2. Academic Validation
  3. Transient receptor potential ankyrin 1 contributes to the ATP-elicited oxidative stress and inflammation in THP-1-derived macrophage

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

  • Mol Cell Biochem. 2020 Oct;473(1-2):179-192. doi: 10.1007/s11010-020-03818-3.
Chao Tian 1 2 3,  Xiaobo Han 1 3,  Lang He 4,  Feng Tang 1 2 3,  Rongqi Huang 1 3,  Zuoxian Lin 1 3,  Shuai Li 1 3,  Sihao Deng 5,  Junjie Xu 2,  Hualin Huang 1 3,  Huifang Zhao 1 3,  Zhiyuan Li 6 7 8 9 10
Affiliations

Affiliations

  • 1 Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China.
  • 2 Guangzhou JYK Biotechnology Company Limited, Guangzhou, Guangdong, China.
  • 3 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China.
  • 4 Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 5 Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
  • 6 Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China. [email protected].
  • 7 Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China. [email protected].
  • 8 Guangzhou JYK Biotechnology Company Limited, Guangzhou, Guangdong, China. [email protected].
  • 9 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China. [email protected].
  • 10 GZMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China. [email protected].
PMID: 32627113 DOI: 10.1007/s11010-020-03818-3
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.

Keywords

ATP; IL-1β; Macrophage; P2X7R; ROS; TRPA1.

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