from 01.01.2023 until now
Kirov Military Medical Academy
Saint Petersburg, St. Petersburg, Russian Federation
Saint Petersburg, St. Petersburg, Russian Federation
Store-operated Ca2+ entry (SOCE) is the ubiquitous mechanism of regulated Ca2+-entry in eukaryotic cells, activated upon depletion of intracellular Ca2+-stores; participates in regulation of a wide range of cellular processes (exocytosis, gene expression, etc.). After discovery of the important role of SOCE in the pathogenesis of human diseases, such as severe combined immunodeficiency, nasal polyposis, etc., the researcher’s interest in the development of low molecular weight blockers of SOCE increased. To determine the pharmacological characteristics of SOCE in macrophages, it seemed appropriate to study the effect of the pyrazole derivative compound YM-58483 on SOCE induced by endoplasmic Ca2+-ATPase inhibitors thapsigargin and cyclopiazonic acid (CPA) in rat peritoneal macrophages. Using Fura-2AM microfluorimetry we found that upon addition of YM-58483 during the developed SOCE induced by thapsigargin or CPA almost complete inhibition of SOCE was observed. This suggests that YM-58483 effectively suppresses already developed SOCE in macrophages. In the second series of experiments, we investigated the effect of YM-58483 after Ca2+ entry mechanisms were activated by store depletion. Macrophages were stimulated by CPA or thapsigargin in Ca2+-free medium. After Ca2+-mobilization from the stores, the cells were incubated for 5 min with YM-58483, then Ca2+ entry into the cell was initiated. It was found that under these conditions, YM-58483 also causes a significant suppression of SOCE. Thus, we showed for the first time on rat peritoneal macrophages, that pyrazole derivative YM-58483 effectively inhibits SOCE and is a useful pharmacological tool for studying SOCE in macrophages, as well as in other cell types.
pyrazole derivative compound YM-58483, store-operated Ca2+ entry, peritoneal macrophages
1. Putney J.W. Capacitative calcium entry revisited. Cell Calcium, 1990. vol. 11, pp. 611-624.
2. Putney J.W. Store-operated calcium entry: a historical overview. Adv. Exp. Med. Biol., 2017, vol. 981, pp. 205-214.
3. Putney J. W. The physiological function of store-operated calcium entry. Neurochem. Res., 2011., vol. 36, pp. 1157-1165.
4. Prakriya M., Lewis R.S. Store-operated calcium channels. Physiol. Rev., 2015, vol. 95, pp. 1383-1436.
5. Vaca L. SOCIC: the store-operated calcium influx complex. Cell Calcium., 2010, vol. 47, pp. 199-209.
6. Moreno C., Vaca L. Microdomain organization of SOCE signaling. In: Store-operated Ca2+ entry (SOCE) pathways. Wien: Springer-Verlag, 2012, pp. 93-113.
7. Nwokonko R.M., Cai X., Loktionova N.A., Wang Y., Zhou Y., Gill D.L. The STIM-Orai pathway: conformational coupling between STIM and Orai in the activation of store-operated Ca2+ entry. Adv. Exp. Med. Biol., 2017, vol. 993, pp. 83-98.
8. Nguyen N.T., Han W., Cao W.-M., Wang Y., Wen S., Huang Y., Li M., Du L., Zhou Y. Store-operated calcium entry mediated by ORAI and STIM. Comprehensive Physiol., 2018, vol. 8, pp. 981-1002.
9. Lunz V., Romanin C., Frischauf I. STIM1 activation of Orai1. Cell Calcium, 2019, vol. 77, pp. 29-38.
10. Shaw P.J., Feske St. Physiological and pathophysiological functions of SOCE in the immune system. Front. Biosci., 2013, vol. 4, pp. 2253-2268.
11. Lacruz R.S., Feske St. Diseases caused by mutations in ORAI1 and STIM1. Ann. N.Y. Acad. Sci., 2015, vol. 1356, pp. 45-79.
12. Feske St. CRAC channels and disease - From human CRAC channelopathies and animal models to novel drugs. Cell Calcium, 2019, vol. 80, pp. 112-116.
13. Ishikawa J., Ohga K., Yoshino T., Takezawa R., Ichikawa A., Kubota H., Yamada T. A pyrazole derivative, YM-58483, potently inhibits store-operated sustained Ca2+ influx and IL-2 production in T lymphocytes. J. Immunol., 2003, vol. 170, pp. 4441-4449.
14. Milenina L.S., Kruteckaya Z.I., Naumova A.A., Butov S.N., Kruteckaya N.I., Antonov V.G. Ingibitory metabolizma arahidonovoy kisloty podavlyayut Sa2+otvety, vyzyvaemye trifluoperazinom, v makrofagah. Citologiya, 2018, t. 60, nomer 2, s. 116-121. @@[Milenina L.S., Krutetskaya Z.I., Naumova A.A., Butov S.N., Krutetskaya N.I., Antonov V.G. Arachidonic acid metabolism inhibitors attenuate Ca2+ responses induced by trifluoperazine in macrophages. Cell Tissue Biol., 2018, vol. 12, no. 4, pp. 315-322. (In Russ.)]
15. Grynkiewicz G., Poenie M., Tsien R.Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem., 1985, vol. 260, pp. 3440-3450.
16. Xie Q., Zhang Y., Zhai C., Bonanno J. A. Calcium influx factor from cytochrome P-450 metabolism and secretion-like coupling mechanisms for capacitative calcium entry in corneal endothelial cells. J. Biol. Chem., 2002, vol. 277, pp. 16559-16566.
17. Xia J., Pan R., Gao X., Meucci O., Hu H. Native store-operated calcium channels are functionally expressed in mouse spinal cord dorsal horn neurons and regulate resting calcium homeostasis. J. Physiol., 2014, vol. 592.16, pp. 3443-3461.
18. Zeng B., Chen G.-L., Garcia-Vaz E., Bhandari S., Daskoulidou N., Berglund L. M., Jiang H., Hallett T., Zhou L.-P., Huang L., Xu Z.-H., Nair V., Nelson R. G., Ju W., Kretzler M., Atkin S. L., Gomez M.F., Xu Sh.-Z. ORAI channels are critical for receptor-mediated endocytosis of albumin. Nat. Commun., 2017, vol. 8, p. 1920, DOI:https://doi.org/10.1038/s41467-017-02094-y.
19. Kimura M., Nishi K., Higashikawa A., Ohyama S., Sakurai K., Tazaki M., Shibukawa Y. High pH-sensitive store-operated Ca2+ entry mediated by Ca2+ release-activated Ca2+ channels in rat odontoblasts. Front. Physiol., 2018, vol. 9, p. 443. DOI:https://doi.org/10.3389/fphys.2018.00443.
20. Rahman S., Rahman T. Unveiling some FDA-approved drugs as inhibitors of the store-operated Ca2+ entry pathway. Sci. Rep., 2017, vol. 7, p. 12881. DOI:https://doi.org/10.1038/s41598-017-13343-x.
21. Sadaghiani A.M., Lee S.M., Odegaard J.I., Leveson-Gower D.B., McPherson O.M., Novick P., Kim M.R., Koehler A.N., Negrin R., Dolmetsch R.E., Park Ch.Y. Identification of Orai1 channel inhibitors by using minimal functional domains to screen small molecule microarrays. Chem. Biol., 2014, vol. 21, pp. 1278-1292.
22. Derler I., Schindl R., Fritsch R., Heftberger P., Riedl M.Ch., Begg M., House D., Romanin Ch. The action of selective CRAC channel blockers is affected by the Orai pore geometry. Cell Calcium, 2013, vol. 53, pp. 139-151.
23. Jairaman A., Prakriya M. Molecular pharmacology of store-operated CRAC channels. Channels, 2013, vol. 7, pp. 402-414.
