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
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瞬时受体电位锚蛋白 1 有助于 THP-1 衍生巨噬细胞中 ATP 引发的氧化应激和炎症
DOI：
10.1007/s11010-020-03818-3
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发表时间：
2020-07
影响因子：
4.3
通讯作者：
Zhiyuan Li
中科院分区：
文献类型：
--
作者：
Chao Tian;Xiaobo Han;Lang He;Feng Tang;Rongqi Huang;Zuoxian Lin;Shuai Li;Sihao Deng;Junjie Xu;Hualin Huang;Huifang Zhao;Zhiyuan Li
P2X7受体(P2X7R)是一种ATP门控的非选择性阳离子通道，介导了ATP诱导的巨噬细胞炎症反应。瞬时受体电位(TRP)受体是细胞膜上感知环境刺激物刺激的伤害性感受器。色氨酸通道与P2X7R之间的相互作用已被发现，但有关炎症的细节仍不清楚。在本研究中，我们认为Trp超家族成员瞬时受体潜在锚蛋白1(TRPA1)参与了ATP诱导的人急性单核细胞白血病细胞系(THP-1)来源的巨噬细胞的氧化应激和炎症反应。用免疫荧光法检测TRPA1和P2X7R在THP-1来源的巨噬细胞和转染人胚胎肾细胞系(HEK293T)中的共定位。通过钙离子成像、线粒体活性氧测定、线粒体膜电位(∆Ψm)测定、流式细胞术、酶联免疫吸附试验、Western blotting、CCK-8测定和乳酸脱氢酶释放细胞毒试验，证实了三磷酸腺苷或3‘-O-(4-苯甲酰基苯甲酰基)三磷酸腺苷(BzATP)诱导巨噬细胞活化的机制。三磷酸腺苷和三磷酸腺苷引起的细胞内钙超载、线粒体损伤、白细胞介素1β(IL-1β)的分泌以及细胞毒作用均可被TRPA1拮抗剂抑制。这些结果表明，TRPA1可以与P2X7R共定位，并介导ATP诱导的氧化应激和炎症反应。因此，抑制TRPA1可能为ATP诱导的包括动脉粥样硬化在内的炎症性疾病提供一种潜在的治疗方法。
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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炎症过程中的核苷酸信号传导。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.4
作者：
Janks, Laura;Sprague, Randy S.;Egan, Terrance M.
通讯作者：
Egan, Terrance M.
影响因子：
3.1
作者：
Hajna, Zsfia;Saghy, Eva;Pinter, Erika
通讯作者：
Pinter, Erika
DOI：
10.1161/atvbaha.115.306964
发表时间：
2016-06
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Li X;Fang P;Li Y;Kuo YM;Andrews AJ;Nanayakkara G;Johnson C;Fu H;Shan H;Du F;Hoffman NE;Yu D;Eguchi S;Madesh M;Koch WJ;Sun J;Jiang X;Wang H;Yang X
通讯作者：
Yang X
影响因子：
5.4
作者：
Peng K;Liu L;Wei D;Lv Y;Wang G;Xiong W;Wang X;Altaf A;Wang L;He D;Wang H;Qu P
通讯作者：
Qu P