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.

该研究探讨了 U87-MG 胶质母细胞瘤细胞的焦亡是否可能由局部麻醉剂激活 Ca ²⁺ /钙调蛋白依赖性蛋白激酶 II (CaMKII) 引起的问题。暴露于不同浓度的典型局部麻醉剂利多卡因的胶质母细胞瘤细胞表现出增加的 Ca ²⁺细胞溶质通量，而用相应的 siRNA 抑制 CaMKII 表达显着抑制了用 2 mM 利多卡因处理的细胞中的这种效应。利多卡因上调 mRNA caspase-3 和 gasdermin GSDME 蛋白的表达，而用 siRNA 沉默 CaMKII 基因显着缓和了这种作用。此外，利多卡因抑制 U87-MG 细胞的增殖，而这种作用可以通过沉默 CaMKII 基因来防止。因此，利多卡因激活蛋白激酶 CaMKII，磷酸化 TRPV1 离子通道并诱导 U87-MG 胶质母细胞瘤细胞的钙超载，从而引发细胞焦亡。