The study examines the problem whether pyroptosis of U87-MG glioblastoma cells can result from activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) by a local anesthetic. Glioblastoma cells exposed to various concentrations of typical local anesthetic lidocaine demonstrated augmented cytosolic flux of Ca2+, while suppression of CaMKII expression with the corresponding siRNA significantly inhibited this effect in cells treated with 2 mM lidocaine. Lidocaine up-regulated the expression of mRNA caspase-3 and gasdermin GSDME proteins, whereas silencing of CaMKII gene with siRNA significantly moderated this effect. In addition, lidocaine inhibited proliferation of U87-MG cells, and this effect was prevented by silencing CaMKII gene. Thus, lidocaine activated protein kinase CaMKII, which phosphorylated TRPV1 ion channels and induced calcium overload of U87-MG glioblastoma cells, thereby provoking their pyroptosis.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 171, No. 3, pp. 273-281, March, 2021
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Zhou, B., Lin, Y., Chen, S. et al. Activation of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII) with Lidocaine Provokes Pyroptosis of Glioblastoma Cells. Bull Exp Biol Med 171, 297–304 (2021). https://doi.org/10.1007/s10517-021-05216-1
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DOI: https://doi.org/10.1007/s10517-021-05216-1