Department of Pharmaceutical Botany, Hebei University of Chinese Medicine, Shijiazhuang, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Biochim Biophys Acta Mol Basis Dis. 2017 Jul;1863(7):1829-1839. doi: 10.1016/j.bbadis.2017.05.001. Epub 2017 May 3.
Hexokinase-II (HK-II) confers protection against cell death and this study was designed to investigate the effect of mangiferin on the regulation of mitochondrial HK-II. In vessel endothelial cells, saturated fatty acid palmitate (PA) stimulation induced HK-II detachment from mitochondria due to cellular acidification. Mangiferin reduced lactate accumulation by improving pyruvate dehydrogenase activity, promoted Akt translocation to HK-II and prevented HK-II detachment from mitochondria. Knockdown of Akt2 diminished the protective effect of mangiferin on mitochondrial HK-II, confirming the role of Akt in the regulation of HK-II. Mangiferin prevented mitochondrial permeability transition pore opening, restored mitochondrial membrane potential and thereby protected cell from apoptosis. In high-fat diet fed mice, oral administration of mangiferin induced Akt phosphorylation, increased HK-II binding to mitochondria and resultantly protected vessel endothelial function, demonstrating its protective effect on endothelial integrity in vivo. This finding provided a novel strategy for the protection of mitochondrial function in the endothelium.
己糖激酶-II（HK-II）可提供细胞死亡保护，本研究旨在探讨芒果苷对调节线粒体 HK-II 的影响。在血管内皮细胞中，饱和脂肪酸棕榈酸（PA）刺激由于细胞酸化而导致 HK-II 从线粒体上脱离。芒果苷通过改善丙酮酸脱氢酶活性减少乳酸积累，促进 Akt 向 HK-II 的易位，并防止 HK-II 从线粒体上脱离。Akt2 的敲低削弱了芒果苷对线粒体 HK-II 的保护作用，证实了 Akt 在调节 HK-II 中的作用。芒果苷防止线粒体通透性转换孔打开，恢复线粒体膜电位，从而防止细胞凋亡。在高脂饮食喂养的小鼠中，芒果苷的口服给予诱导 Akt 磷酸化，增加 HK-II 与线粒体的结合，从而保护血管内皮功能，证明其在体内对内皮完整性的保护作用。这一发现为保护内皮细胞中线粒体功能提供了一种新策略。
