1. Makale, M. T., McDonald, C. R., Hattangadi-Gluth, J. A. & Kesari, S. Mechanisms of radiotherapy-associated cognitive disability
in patients with brain tumours. Nat. Rev. Neurol. 13, 52–64 (2017).
2. Zhuang, H., Siyu, S., Yuan, Z. & Chang, J. Y. Bevacizumab treatment for radiation brain necrosis: Mechanism, efficacy and issues.
Mol. Cancer 18, 21 (2019).
3. Makide, K., Kitamura, H., Sato, Y., Okutani, M. & Aoki, J. Emerging lysophospholipid mediators, lysophosphatidylserine, lysophosphatidylthreonine, lysophosphatidylethanolamine and lysophosphatidylglycerol. Prostagland. Other Lipid Mediat. 89, 135–213
(2009).
4. Wang, C., Yang, J. & Nie, J. Plasma phospholipid metabolic profiling and biomarkers of rats following radiation exposure based
on liquid chromatography-mass spectrometry technique. Biomed. Chromatogr. 10, 1079–1085 (2009).
5. Zhao, H. et al. Identification of potential radiation responsive metabolic biomarkers in plasma of rats exposed to different doses
of cobalt-60 gamma rays. Dose Response 18, 1559325820979570 (2020).
6. Upadhyay, M. et al. Identification of plasma lipidome changes associated with low dose space-type radiation exposure in a murine
model. Metabolites 10, 252 (2020).
7. Kondo, N. et al. Localized radiation necrosis model in mouse brain using proton ion beams. Appl. Radiat. Isot. 106, 242–246 (2015).
8. Takata, T. et al. Localized dose delivering by ion beam irradiation for experimental trial of establishing brain necrosis model. Appl.
Radiat. Isot. 105, 32–34 (2015).
9. Ueda, H., Matsunaga, H., Olaposi, O. I. & Nagai, J. Lysophosphatidic acid: Chemical signature of neuropathic pain. Biochem.
Biophys. Acta 1831, 61–73 (2013).
Scientific Reports |
Vol:.(1234567890)
(2022) 12:8718 |
https://doi.org/10.1038/s41598-022-12293-3
12
www.nature.com/scientificreports/
A Self-archived copy in
Kyoto University Research Information Repository
https://repository.kulib.kyoto-u.ac.jp
10. Heneka, M. T. et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 14(4), 388–405 (2015).
11. Inose, Y., Kato, Y., Kitagawa, K., Uchiyama, S. & Shibata, N. Activated microglia in ischemic stroke penumbra upregulate MCP-1
and CCR2 expression in response to lysophosphatidylcholine derived from adjacent neurons and astrocytes. Neuropathology 35,
209–223 (2015).
12. Kabarowski, J. H., Zhu, K., Le, L. Q., Witte, O. N. & Xu, Y. Lysophosphatidylcholine as a ligand for the immunoregutatory receptor
G2A. Science 293, 702–705 (2001).
13. Takenouchi, T., Sato, M. & Kitani, H. Lysophosphatidylcholine potentiates Ca2+ influx, pore formation and p44/42 MAP kinase
phosphorylation mediated by P2X7 receptor activation in mouse microglial cells. J. Neurochem. 102, 1518–1532 (2007).
14. Zabala, A. et al. P2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis. EMBO Mol.
Med. 10, e8743 (2018).
15. Andries, M., Van Damme, P., Robberecht, W. & Van Den Bosch, L. Ivermectin inhibits AMPA receptor-mediated excitotoxicity
in cultured motor neurons and extends the life span of a transgenic mouse model of amyotrophic lateral sclerosis. Neurobiol. Dis.
25, 8–16 (2007).
16. Kitamura, C. et al. The component changes of lysophospholipid mediators in colorectal cancer. Tumour Biol. 41, 1010428319848616
(2019).
17. Morishige, J. et al. A clean-up technology for the simultaneous determination of lysophosphatidic acid and sphingosine-1-phosphate by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using a phosphate-capture molecule, Phostag. Rapid Commun. Mass Spectrom. 24, 1075–1084 (2010).
18. Kurano, M. et al. Possible involvement of minor lysophospholipids in the increase in plasma lysophosphatidic acid in acute coronary
syndrome. Arterioscler. Thromb. Vasc. Biol. 35, 463–470 (2015).
19. Li, X. et al. Mitochondrial reactive oxygen species mediate lysophosphatidylcholine-induced endothelial cell activation. Arterioscler.
Thromb. Vasc. Biol. 36, 1090–1100 (2016).
20. Shao, Y. et al. Lysophospholipids and their receptors serve as conditional DAMPs and DAMP receptors in tissue oxidative and
inflammatory injury. Antioxid. Redox Signal. 28, 973–986 (2018).
21. Frasch, S. C. & Bratton, D. L. Emerging roles for lysophosphatidylserine in resolution of inflammation. Prog. Lipid Res. 51, 199–207
(2012).
22. Hung, N. D., Kim, M. R. & Sok, D. E. 2-Polyunsaturated acyl lysophosphatidylethanolamine attenuates inflammatory response in
zymosan A-induced peritonitis in mice. Lipids 46, 893–906 (2011).
23. Yung, Y. C., Stoddard, N. C., Mirendil, H. & Chun, J. Lysophosphatidic acid signaling in the nervous system. Neuron 85, 669–682
(2015).
24. Choi, J. W. et al. LPA receptors: Subtypes and biological actions. Annu. Rev. Pharmacol. Toxicol. 50, 157–186 (2010).
25. Bommiasamy, H. et al. ATF6alpha induces XBP1-independent expansion of the endoplasmic reticulum. J. Cell Sci. 122, 1626–1636
(2009).
26. Li, W. et al. Crosstalk between ER stress, NLRP3 inflammasome, and inflammation. Appl. Microbiol. Biotechnol. 104, 6129–6140
(2020).
27. Parker, A. G. et al. The effects of IQPLUS focus on cognitive function, mood and endocrine response before and following acute
exercise. J. Int. Soc. Sports Nutr. 21(8), 16 (2011).
28. Yoshida, K., Terao, J., Suzuki, T. & Takama, K. Inhibitory effect of phosphatidylserine on iron-dependent lipid peroxidation.
Biochem. Biophys. Res. Commun. 179, 1077–1081 (1991).
29. Tyurina, Y. Y. et al. Oxidative lipidomics of γ-radiation-induced lung injury: Mass spectrometric characterization of cardiolipin
and phosphatidylserine peroxidation. Radiat. Res. 175, 610–621 (2011).
30. Montilla, A., Mata, G. P., Matute, C. & Domercq, M. Contribution of P2X4 receptors to CNS function and pathophysiology. Int.
J. Mol. Sci. 21, 5562 (2020).
31. Hall, S. M. The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord. J. Cell Sci. 10,
535–546 (1972).
32. Freeman, L. et al. NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes. J. Exp.
Med. 214, 1351–1370 (2017).
33. Scholz, H. & Eder, C. Lysophosphatidylcholine activates caspase-1 in microglia via a novel pathway involving two inflammasomes.
J. Neuroimmunol. 310, 107–110 (2017).
34. Ismaeel, S. & Qadri, A. ATP release drives inflammation with lysophosphatidylcholine. ImmunoHorizons 5, 219–233 (2021).
35. Yagami, T., Yamamoto, Y. & Koma, H. The role of secretory phospholipaseA2 in the central nervous system and neurological
diseases. Mol. Neurobiol. 49, 863–876 (2014).
36. Hoda, M. N., Singh, I., Singh, A. K. & Khan, M. Reduction of lipoxidative load by secretory phospholipase A2 inhibition protects
against neurovascular injury following experimental stroke in rat. J. Neuroinflamm. 6, 21 (2009).
37. Yamakawa, T. et al. Lysophosphatidylcholine activates extracellular signal-regulated kinases 1/2 through reactive oxygen species
in rat vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 22, 752–758 (2002).
Acknowledgements
This research was performed in collaboration with the Radioisotope Research Center, Kyoto University.
Author contributions
N.K. designed the study, conducted the radiation necrosis experiments, supervised all experiments, analyzed and
interpreted the data, and wrote the manuscript. Y.S. and T.T. conducted the radiation necrosis model experiments
and supervised the dose measurements. K.Kano performed the LC–MS/MS analyses and J.A. supervised the LC–
MS/MS experiments. K.Kume and M.M. performed and supervised the proton beam irradiation. N.T. conducted
and supervised the animal behavioral tests. S.S. and H.W. conducted and supervised the immunohistochemical
experiments. F.E., K.Kikushima, and M.Setou conducted and supervised the MALDI-IMS analyses. S.-I.M. and
M.Suzuki helped with the immunohistochemical experiments and advised from the viewpoint of clinical relevance. T.K. and S.O. conducted and supervised immunohistochemistry experiments for Supplementary Figures.
Funding
This research was supported by the Japan Society for the Promotion of Science KAKENHI Grant Number
17K16641 (AdAMS) and the Ishizue Research Development Program of Kyoto University to N.K., the Collaborative Research Grant of the Wakasa Wan Energy Research Center to N.K. and Y.S., and the Japan Society for the
Promotion of Science KAKENHI Grant Number 26293327 to S.-I.M..
Scientific Reports |
(2022) 12:8718 |
https://doi.org/10.1038/s41598-022-12293-3
13
Vol.:(0123456789)
www.nature.com/scientificreports/
A Self-archived copy in
Kyoto University Research Information Repository
https://repository.kulib.kyoto-u.ac.jp
Competing interests The authors declare no competing interests.
Additional information
Supplementary Information The online version contains supplementary material available at https://doi.org/
10.1038/s41598-022-12293-3.
Correspondence and requests for materials should be addressed to N.K.
Reprints and permissions information is available at www.nature.com/reprints.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and
institutional affiliations.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or
format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the
Creative Commons licence, and indicate if changes were made. The images or other third party material in this
article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2022
Scientific Reports |
Vol:.(1234567890)
(2022) 12:8718 |
https://doi.org/10.1038/s41598-022-12293-3
14
...
論文の公開元へ
