Background Ca2+ channels are abnormally expressed in various tumor cells and are involved in the progression of human glioma. Here, we explored the role of a calcium channel, voltage-dependent, T-type, alpha 1H subunit (CACNA1H), which encodes T-type Ca2+ channel Cav3.2 in glioma cells. Methods Cell viability and apoptosis were detected using cell-counting kit-8 and flow cytometry, respectively. The expression of target protein was determined using western blot analysis. Results Cell viability of U251 cells was inhibited significantly after the knockdown of CACNA1H. The apoptosis of U251 cells was enhanced significantly after the knockdown of CACNA1H. Importantly, knockdown of CACNA1H decreased the levels of p-PERK, GRP78, CHOP, and ATF6, indicating that CACNA1H knockdown activated endoplasmic reticulum stress (ERS) in U251 cells. In addition, T-type Ca2+ channel inhibitor NNC55-0396 also induced apoptosis through the activation of ERS in U251 cells. ERS inhibitor UR906 could block CACNA1H inhibitor ABT-639-induced apoptosis. Conclusion Suppression of CACNA1H activated the ERS and thus induced apoptosis in glioma cells. T-type Ca2+ channel inhibitors ABT-639 and NNC55-0396 also induced apoptosis through ERS in glioma cells. Our data highlighted the effect of CACNA1H as an oncogenic gene in human glioma.

中文翻译：

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CACNA1H 的失活通过启动神经胶质瘤中的内质网应激诱导细胞凋亡。

背景 Ca2+ 通道在多种肿瘤细胞中异常表达，并参与人胶质瘤的进展。在这里，我们探索了电压依赖性 T 型钙通道 alpha 1H 亚基 (CACNA1H) 的作用，它在神经胶质瘤细胞中编码 T 型 Ca2+ 通道 Cav3.2。方法分别采用cell-counting kit-8和流式细胞术检测细胞活力和凋亡。使用蛋白质印迹分析确定靶蛋白的表达。结果敲低CACNA1H后，U251细胞的细胞活力受到显着抑制。敲低CACNA1H后，U251细胞的凋亡显着增强。重要的是，CACNA1H 的敲低降低了 p-PERK、GRP78、CHOP 和 ATF6 的水平，表明 CACNA1H 敲低激活了 U251 细胞中的内质网应激 (ERS)。此外，T 型 Ca2+ 通道抑制剂 NNC55-0396 也通过激活 U251 细胞中的 ERS ​​诱导细胞凋亡。ERS 抑制剂 UR906 可以阻断 CACNA1H 抑制剂 ABT-639 诱导的细胞凋亡。结论 抑制CACNA1H可激活ERS，从而诱导胶质瘤细胞凋亡。T 型 Ca2+ 通道抑制剂 ABT-639 和 NNC55-0396 也通过 ERS ​​在神经胶质瘤细胞中诱导细胞凋亡。我们的数据突出了 CACNA1H 作为人类胶质瘤致癌基因的作用。