Transient receptor potential ankyrin 1 contributes to the ATP-elicited oxidative stress and inflammation in THP-1-derive
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Transient receptor potential ankyrin 1 contributes to the ATP‑elicited oxidative stress and inflammation in THP‑1‑derived macrophage Chao Tian1,3,4 · Xiaobo Han1,4 · Lang He6 · Feng Tang1,3,4 · Rongqi Huang1,4 · Zuoxian Lin1,4 · Shuai Li1,4 · Sihao Deng2 · Junjie Xu3 · Hualin Huang1,4 · Huifang Zhao1,4 · Zhiyuan Li1,2,3,4,5 Received: 25 March 2020 / Accepted: 27 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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 TRPA1 · ATP · P2X7R · Macrophage · ROS · IL-1β
Introduction
* Zhiyuan Li [email protected] 1
Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China
2
Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
3
Guangzhou JYK Biotechnology Company Limited, Guangzhou, Guangdong, China
4
Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China
5
GZMU‑GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China
6
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Besides the major energy source for cellular metabolism, ATP is considered as a “fine me” signal molecule when the tissue injury or metabolic disorder happens [1, 2]. In the early stage of hypertension and atherosclerosis, ATP concentration rises i
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