Activation of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII) with Lidocaine Provokes Pyroptosis of Glioblastoma Cells.

Abstract

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.

• Authors: B Zhou, Y Lin, S Chen, J Cai, Z Luo, S Yu, J Lu
• Journal: Bulletin of experimental biology and medicine (Bull Exp Biol Med) Vol. 171 Issue 3 Pg. 297-304 (Jul 2021) ISSN: 1573-8221 [Electronic] United States
• PMID: 34302204 (Publication Type: Journal Article)
• Copyright: © 2021. Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Anesthetics, Local
• GSDME protein, human
• RNA, Small Interfering
• Receptors, Estrogen
• TRPV Cation Channels
• TRPV1 protein, human
• Lidocaine
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• CASP3 protein, human
• Caspase 3
• Calcium

Topics

• Anesthetics, Local (pharmacology)
• Calcium (metabolism)
• Calcium Signaling
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (antagonists & inhibitors, genetics, metabolism)
• Caspase 3 (genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Gene Expression Regulation
• Humans
• Ion Transport (drug effects)
• Lidocaine (pharmacology)
• Neuroglia (cytology, drug effects, metabolism)
• Phosphorylation (drug effects)
• Pyroptosis (drug effects, genetics)
• RNA, Small Interfering (genetics, metabolism)
• Receptors, Estrogen (genetics, metabolism)
• TRPV Cation Channels (genetics, metabolism)