Advertisement

The Journal of Membrane Biology

, Volume 253, Issue 1, pp 43–55 | Cite as

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

  • Chao Tian
  • Rongqi Huang
  • Feng Tang
  • Zuoxian Lin
  • Na Cheng
  • Xiaobo Han
  • Shuai Li
  • Peng Zhou
  • Sihao Deng
  • Hualin Huang
  • Huifang Zhao
  • Junjie Xu
  • Zhiyuan LiEmail author
Article

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.

Graphic Abstract

Keywords

TRPA1 LPC Reactive oxygen species Mitochondria Macrophage Calcium 

Notes

Acknowledgements

This work was supported by the Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Grant No. 2018GZR110105020 and the Guangdong Provincial Natural Science Foundation (2017A030313757 and 2016A030313170), the National Natural Science Foundation of China (31671211). The kind gift of the THP-1 cell line from Dr. Peng Li, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, China, is deeply appreciated.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Bertin S, Aoki-Nonaka Y, Lee J, de Jong PR, Kim P, Han T, Yu T, To K, Takahashi N, Boland BS, Chang JT, Ho SB, Herdman S, Corr M, Franco A, Sharma S, Dong H, Akopian AN, Raz E (2017) The TRPA1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1. Gut 66:1584–1596.  https://doi.org/10.1136/gutjnl-2015-310710 CrossRefPubMedGoogle Scholar
  2. Bodkin JV, Thakore P, Aubdool AA, Liang L, Fernandes ES, Nandi M, Spina D, Clark JE, Aaronson PI, Shattock MJ, Brain SD (2014) Investigating the potential role of TRPA1 in locomotion and cardiovascular control during hypertension. Pharmacol Res Perspect 2:e00052.  https://doi.org/10.1002/prp2.52 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Cha MH, Lee SM, Jung J (2018) Lysophosphatidylcholine induces expression of genes involved in cholesterol biosynthesis in THP-1 derived macrophages. Steroids 139:28–34.  https://doi.org/10.1016/j.steroids.2018.09.003 CrossRefPubMedGoogle Scholar
  4. De Logu F, Nassini R, Materazzi S, Carvalho Goncalves M, Nosi D, Degl’Innocenti DR, Marone IM, Ferreira J, Li Puma S, Benemei S, Trevisan G, Monteiro Souza, de Araujo D, Patacchini R, Bunnett NW, Geppetti P (2017) Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice. Nat Commun 8:1887.  https://doi.org/10.1038/s41467-017-01739-2 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Deveci HA, Akyuva Y, Nur G, Naziroglu M (2019) Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line. Biomed Pharmacother 111:292–304.  https://doi.org/10.1016/j.biopha.2018.12.077 CrossRefPubMedGoogle Scholar
  6. Fang L, Green SR, Baek JS, Lee SH, Ellett F, Deer E, Lieschke GJ, Witztum JL, Tsimikas S, Miller YI (2011) In vivo visualization and attenuation of oxidized lipid accumulation in hypercholesterolemic zebrafish. J Clin Invest 121:4861–4869.  https://doi.org/10.1172/jci57755 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Freeman L, Guo H, David CN, Brickey WJ, Jha S, Ting JP (2017) NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes. J Exp Med 214:1351–1370.  https://doi.org/10.1084/jem.20150237 CrossRefPubMedPubMedCentralGoogle Scholar
  8. He Y, Hara H, Nunez G (2016) Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci 41:1012–1021.  https://doi.org/10.1016/j.tibs.2016.09.002 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Jeong H, Kim YH, Lee Y, Jung SJ, Oh SB (2017) TRPM2 contributes to LPC-induced intracellular Ca(2+) influx and microglial activation. Biochem Biophys Res Commun 485:301–306.  https://doi.org/10.1016/j.bbrc.2017.02.087 CrossRefPubMedGoogle Scholar
  10. Jiang Y, Wang M, Huang K, Zhang Z, Shao N, Zhang Y, Wang W, Wang S (2012) Oxidized low-density lipoprotein induces secretion of interleukin-1beta by macrophages via reactive oxygen species-dependent NLRP3 inflammasome activation. Biochem Biophys Res Commun 425:121–126.  https://doi.org/10.1016/j.bbrc.2012.07.011 CrossRefPubMedGoogle Scholar
  11. Jung H-J, Im S-S, Song D-K, Bae J-H (2017) Effects of chlorogenic acid on intracellular calcium regulation in lysophosphatidylcholine-treated endothelial cells. BMB Rep 50:323–328.  https://doi.org/10.5483/BMBRep.2017.50.6.182 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Khalil M, Alliger K, Weidinger C, Yerinde C, Wirtz S, Becker C, Engel MA (2018) Functional role of transient receptor potential channels in immune cells and epithelia. Front Immunol 9:174.  https://doi.org/10.3389/fimmu.2018.00174 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Kinard F, Jaworski K, Sergent-Engelen T, Goldstein D, Van Veldhoven PP, Holvoet P, Trouet A, Schneider YJ, Remacle C (2001) Smooth muscle cells influence monocyte response to LDL as well as their adhesion and transmigration in a coculture model of the arterial wall. J Vasc Res 38:479–491.  https://doi.org/10.1159/000051081 CrossRefPubMedGoogle Scholar
  14. 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 (2016) Mitochondrial reactive oxygen species mediate lysophosphatidylcholine-induced endothelial cell activation. Arterioscler Thromb Vasc Biol 36:1090–1100.  https://doi.org/10.1161/ATVBAHA.115.306964 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Liu-Wu Y, Hurt-Camejo E, Wiklund O (1998) Lysophosphatidylcholine induces the production of IL-1beta by human monocytes. Atherosclerosis 137:351–357CrossRefGoogle Scholar
  16. Matsumoto T, Kobayashi T, Kamata K (2007) Role of lysophosphatidylcholine (LPC) in atherosclerosis. Curr Med Chem 14:3209–3220CrossRefGoogle Scholar
  17. Nowak WN, Deng J, Ruan XZ, Xu Q (2017) Reactive oxygen species generation and atherosclerosis. Arterioscler Thromb Vasc Biol 37:e41–e52.  https://doi.org/10.1161/ATVBAHA.117.309228 CrossRefPubMedGoogle Scholar
  18. Rayamajhi M, Zhang Y, Miao EA (2013) Detection of pyroptosis by measuring released lactate dehydrogenase activity. Methods Mol Biol 1040:85–90.  https://doi.org/10.1007/978-1-62703-523-1_7 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Robbesyn F, Salvayre R, Negre-Salvayre A (2004) Dual role of oxidized LDL on the NF-kappaB signaling pathway. Free Radic Res 38:541–551CrossRefGoogle Scholar
  20. Schilling T, Eder C (2009) Non-selective cation channel activity is required for lysophosphatidylcholine-induced monocyte migration. J Cell Physiol 221:325–334.  https://doi.org/10.1002/jcp.21857 CrossRefPubMedGoogle Scholar
  21. Schmitz G, Ruebsaamen K (2010) Metabolism and atherogenic disease association of lysophosphatidylcholine. Atherosclerosis 208:10–18.  https://doi.org/10.1016/j.atherosclerosis.2009.05.029 CrossRefPubMedGoogle Scholar
  22. Seuwen K, Ludwig MG, Wolf RM (2006) Receptors for protons or lipid messengers or both? J Recept Signal Transduct Res 26:599–610.  https://doi.org/10.1080/10799890600932220 CrossRefPubMedGoogle Scholar
  23. Takaya J, Mio K, Shiraishi T, Kurokawa T, Otsuka S, Mori Y, Uesugi M (2015) A potent and site-selective agonist of TRPA1. J Am Chem Soc 137:15859–15864.  https://doi.org/10.1021/jacs.5b10162 CrossRefPubMedGoogle Scholar
  24. Tsai TY, Leong IL, Cheng KS, Shiao LR, Su TH, Wong KL, Chan P, Leung YM (2019) Lysophosphatidylcholine-induced cytotoxicity and protection by heparin in mouse brain bEND.3 endothelial cells. Fundam Clin Pharmacol 33:52–62.  https://doi.org/10.1111/fcp.12399 CrossRefPubMedGoogle Scholar
  25. Wang Z, Wang M, Liu J, Ye J, Jiang H, Xu Y, Ye D, Wan J (2018) Inhibition of TRPA1 attenuates doxorubicin-induced acute cardiotoxicity by suppressing oxidative stress, the inflammatory response, and endoplasmic reticulum stress. Oxid Med Cell Longev 2018:5179468.  https://doi.org/10.1155/2018/5179468 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Wenzel P, Kossmann S, Munzel T, Daiber A (2017) Redox regulation of cardiovascular inflammation—Immunomodulatory function of mitochondrial and Nox-derived reactive oxygen and nitrogen species. Free Radic Biol Med 109:48–60.  https://doi.org/10.1016/j.freeradbiomed.2017.01.027 CrossRefPubMedGoogle Scholar
  27. Yin S, Wang P, Xing R, Zhao L, Li X, Zhang L, Xiao Y (2018a) Transient receptor potential ankyrin 1 (TRPA1) mediates lipopolysaccharide (LPS)-induced inflammatory responses in primary human osteoarthritic fibroblast-like synoviocytes. Inflammation 41:700–709.  https://doi.org/10.1007/s10753-017-0724-0 CrossRefPubMedGoogle Scholar
  28. Yin S, Zhang L, Ding L, Huang Z, Xu B, Li X, Wang P, Mao J (2018b) Transient receptor potential ankyrin 1 (trpa1) mediates il-1beta-induced apoptosis in rat chondrocytes via calcium overload and mitochondrial dysfunction. J Inflamm (Lond) 15:27.  https://doi.org/10.1186/s12950-018-0204-9 CrossRefGoogle Scholar
  29. Yu J, Nagasu H, Murakami T, Hoang H, Broderick L, Hoffman HM, Horng T (2014) Inflammasome activation leads to Caspase-1-dependent mitochondrial damage and block of mitophagy. Proc Natl Acad Sci USA 111:15514–15519.  https://doi.org/10.1073/pnas.1414859111 CrossRefPubMedGoogle Scholar
  30. Zhao J, Xu S, Song F, Nian L, Zhou X, Wang S (2014) 2,3,5,4’-Tetrahydroxystilbene-2-O-beta-d-glucoside protects human umbilical vein endothelial cells against lysophosphatidylcholine-induced apoptosis by upregulating superoxide dismutase and glutathione peroxidase. IUBMB Life 66:711–722.  https://doi.org/10.1002/iub.1321 CrossRefPubMedGoogle Scholar
  31. Zhao JF, Shyue SK, Kou YR, Lu TM, Lee TS (2016) Transient receptor potential ankyrin 1 channel involved in atherosclerosis and macrophage-foam cell formation. Int J Biol Sci 12:812–823.  https://doi.org/10.7150/ijbs.15229 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221–225.  https://doi.org/10.1038/nature09663 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • 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
    • 6
  • Zhiyuan Li
    • 1
    • 2
    • 3
    • 4
    • 5
    Email author
  1. 1.School of Life SciencesUniversity of Science and Technology of ChinaHefeiChina
  2. 2.Key Laboratory of Regenerative BiologyGuangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangzhouChina
  3. 3.Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhouChina
  4. 4.Department of Anatomy and Neurobiology, School of Basic Medical SciencesCentral South UniversityChangshaChina
  5. 5.GZMU-GIBH Joint School of Life SciencesGuangzhou Medical UniversityGuangzhouChina
  6. 6.Guangzhou JYK Biotechnology Company LimitedGuangzhouChina

Personalised recommendations