Sohlang Melinda Nongbet, Majaw Suktilang
Department of Biotechnology and Bioinformatics, North-Eastern Hill University, Shillong, India.
Arch Physiol Biochem. 2023 Jun;129(3):723-733. doi: 10.1080/13813455.2020.1867187. Epub 2021 Jan 12.
Increased apoptotic lymphocytes have been correlated to a high incidence of infection in poorly controlled diabetes. This study aimed to determine whether altered voltage-dependent anion channel (VDAC)-hexokinase (HK) association contributes to the increase in apoptosis. Mouse peripheral blood lymphocytes (PBL) exposed to high glucose (Glc)/palmitic acid (PA) were used as the model, which was compared with PBL isolated from alloxan-induced diabetic mice ( model). Our results showed a significant increase in apoptosis as indicated by the apoptotic index, caspase-3 activity, mitochondrial membrane potential and ultrastructural study. HK and glucose-6-phosphate dehydrogenase (G6PDH) activities were markedly reduced with a profound increase in glucose-6-phosphate level. Co-immunoprecipitation confirms HK interaction with VDAC, an outer mitochondrial membrane protein. Inhibited glycolytic enzyme, i.e. HK and reduced HK-VDAC interaction in our study could contribute to increased apoptosis in lymphocytes exposed to high Glc/PA. Targeting HK-VDAC interaction may therefore provide therapeutic potential for the treatment of diabetes-associated infection.
凋亡淋巴细胞增多与糖尿病控制不佳时感染的高发生率相关。本研究旨在确定电压依赖性阴离子通道（VDAC）-己糖激酶（HK）结合的改变是否导致凋亡增加。将暴露于高葡萄糖（Glc）/棕榈酸（PA）的小鼠外周血淋巴细胞（PBL）用作模型，并与从四氧嘧啶诱导的糖尿病小鼠分离的PBL（模型）进行比较。我们的结果显示，凋亡指数、半胱天冬酶-3活性、线粒体膜电位和超微结构研究表明凋亡显著增加。HK和葡萄糖-6-磷酸脱氢酶（G6PDH）活性显著降低，而葡萄糖-6-磷酸水平显著升高。免疫共沉淀证实HK与线粒体外膜蛋白VDAC相互作用。在我们的研究中，糖酵解酶（即HK）受到抑制且HK-VDAC相互作用减少，这可能导致暴露于高Glc/PA的淋巴细胞凋亡增加。因此，针对HK-VDAC相互作用可能为糖尿病相关感染的治疗提供治疗潜力。
