2. Academic Validation
  3. Transient Receptor Potential Ankyrin 1 Contributes to Lysophosphatidylcholine-Induced Intracellular Calcium Regulation and THP-1-Derived Macrophage Activation

Transient Receptor Potential Ankyrin 1 Contributes to Lysophosphatidylcholine-Induced Intracellular Calcium Regulation and THP-1-Derived Macrophage Activation

  • J Membr Biol. 2020 Feb;253(1):43-55. doi: 10.1007/s00232-019-00104-2.
Chao Tian 1 2 3,  Rongqi Huang 2 3,  Feng Tang 2 3,  Zuoxian Lin 2 3,  Na Cheng 2 3 4,  Xiaobo Han 2 3,  Shuai Li 2 3,  Peng Zhou 4,  Sihao Deng 4,  Hualin Huang 2 3,  Huifang Zhao 1 2 3,  Junjie Xu 5,  Zhiyuan Li 6 7 8 9 10
Affiliations

Affiliations

  • 1 School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
  • 2 Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, #190 Kai-Yuan Road, Guangzhou Science Park, Guangzhou, 510530, China.
  • 3 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China.
  • 4 Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
  • 5 Guangzhou JYK Biotechnology Company Limited, Guangzhou, Guangdong, China.
  • 6 School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China. li_zhiyuan@gibh.ac.cn.
  • 7 Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, #190 Kai-Yuan Road, Guangzhou Science Park, Guangzhou, 510530, China. li_zhiyuan@gibh.ac.cn.
  • 8 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China. li_zhiyuan@gibh.ac.cn.
  • 9 Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China. li_zhiyuan@gibh.ac.cn.
  • 10 GZMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China. li_zhiyuan@gibh.ac.cn.
PMID: 31820013 DOI: 10.1007/s00232-019-00104-2
Abstract

Lysophosphatidylcholine (LPC) is a major atherogenic lipid that stimulates an increase in mitochondrial Reactive Oxygen Species (mtROS) and the release of cytokines under inflammasome activation. However, the potential receptors of LPC in macrophages are poorly understood. Members of the transient receptor potential (TRP) channel superfamily, which is crucially involved in transducing environmental irritant stimuli into nociceptor activity, are potential receptors of LPC. In this study, we investigated whether LPC can induce the activation of transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily. The functional expression of TRPA1 was first detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and calcium imaging in human acute monocytic leukemia cell line (THP-1)-derived macrophages. The mechanism by which LPC induces the activation of macrophages through TRPA1 was verified by cytoplasmic and mitochondrial calcium imaging, mtROS detection, a JC-1 assay, enzyme-linked immunosorbent assay, the CCK-8 assay and the Lactate Dehydrogenase (LDH) cytotoxic assay. LPC induced the activation of THP-1-derived macrophages via calcium influx, and this activation was suppressed by potent and selective inhibitors of TRPA1. These results indicated that TRPA1 can mediate mtROS generation, mitochondrial membrane depolarization, the secretion of IL-1β and cytotoxicity through cellular and mitochondrial CA2+ influx in LPC-treated THP-1-derived macrophages. Therefore, the inhibition of TRPA1 may protect THP-1-derived macrophages against LPC-induced injury.

Keywords

Calcium; LPC; Macrophage; Mitochondria; Reactive oxygen species; TRPA1.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-111132
    99.90%, TRP Channel Agonist