HV1 缺乏通过调节 NOX4 水平保护β细胞免受糖毒性。
Hv1-deficiency protects β cells from glucotoxicity through regulation of NOX4 level.
机构信息
Department of Biophysics, School of Physics Science, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, 300071, PR China.
Key Laboratory of Artificial Cell, Third Central Clinical College of Tianjin Medical University, Tianjin, 300170, PR China.
出版信息
Biochem Biophys Res Commun. 2019 May 28;513(2):434-438. doi: 10.1016/j.bbrc.2019.03.195. Epub 2019 Apr 6.
High glucose (HG)-induced oxidative stress contributes to the dysfunction of pancreatic β cells in diabetes. The voltage-gated proton channel Hv1 has been proposed to support reactive oxygen species (ROS) production during respiratory bursts. However, the effect of Hv1 on glucotoxicity in pancreatic β cells is not clear yet. In this study, we examined the protective effects of Hv1-deficiency in HG cultured β cells. Following 48 h of treatment with 30 mM high glucose, Hv1 KO β cells showed higher cell viability, lower cell apoptosis and a more stable insulin gene expression level compared to WT β cells. In both control and HG cultured β cells, deficiency of Hv1 decreased the glucose- and PMA-induced ROS production. Finally, HG incubation led to NOX4 upregulation in WT β cells, which could be inhibited by HV1 deficiency. In conclusion, Hv1-deficiency prevents the HG treatment-induced NOX4 upregulation and protects β cells from glucotoxicity.
高葡萄糖（HG）诱导的氧化应激导致糖尿病中胰腺β细胞功能障碍。已经提出电压门控质子通道 Hv1 在呼吸爆发期间支持活性氧（ROS）的产生。然而，Hv1 对胰腺β细胞糖毒性的影响尚不清楚。在这项研究中，我们研究了 Hv1 缺失在 HG 培养的β细胞中的保护作用。在 30 mM 高葡萄糖处理 48 小时后，与 WT β细胞相比，Hv1 KO β细胞表现出更高的细胞活力、更低的细胞凋亡和更稳定的胰岛素基因表达水平。在对照和 HG 培养的β细胞中，Hv1 的缺失均降低了葡萄糖和 PMA 诱导的 ROS 产生。最后，HG 孵育导致 WT β细胞中 NOX4 的上调，这种上调可被 Hv1 缺失抑制。总之，Hv1 缺失可防止 HG 处理诱导的 NOX4 上调并保护β细胞免受糖毒性。
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