Koziel Agnieszka, Jarmuszkiewicz Wieslawa
Department of Bioenergetics, Adam Mickiewicz University, Umultowska 89, 61-614, Poznan, Poland.
Pflugers Arch. 2017 Jun;469(5-6):815-827. doi: 10.1007/s00424-017-1935-9. Epub 2017 Feb 8.
The goal of our study was to assess the influence of chronic exposure to hypoxia on mitochondrial oxidative metabolism in human umbilical vein endothelial cells (EA.hy926 line) cultured for 6 days at 1% O tension. The hypoxia-induced effects were elucidated at the cellular and isolated mitochondria levels. Hypoxia elevated fermentation but did not change mitochondrial biogenesis or the aerobic respiratory capacity of endothelial cells. In endothelial cells, hypoxia caused a general decrease in mitochondrial respiration during carbohydrate, fatty acid, and amino acid oxidation but increased exclusively ketogenic amino acid oxidation. Hypoxia induced an elevation of intracellular and mitochondrial reactive oxygen species (ROS) formation, although cell viability was unchanged and antioxidant systems (superoxide dismutases SOD1 and SOD2, and uncoupling proteins (UCPs)) were not increased. In mitochondria from hypoxic cells, the opposite change was observed at the respiratory chain level, i.e., considerably elevated expression and activity of complex II, and decreased expression and activity of complex I were observed. The elevated activity of complex II resulted in an increase in succinate-sustained mitochondrial ROS formation, mainly through increased reverse electron transport. A hypoxia-induced decrease in UCP2 expression and activity was also observed. It can be concluded that the exposure to chronic hypoxia induces a shift from aerobic toward anaerobic catabolic metabolism. The hypoxia-induced increase in intracellular and mitochondrial ROS formation was not excessive and may be involved in endothelial signaling of hypoxic responses. Our results indicate an important role of succinate, complex II, and reverse electron transport in hypoxia-induced adjustments in endothelial cells.
我们研究的目的是评估在1%氧气张力下培养6天的人脐静脉内皮细胞（EA.hy926系）长期暴露于低氧环境对线粒体氧化代谢的影响。在细胞和分离的线粒体水平上阐明了低氧诱导的效应。低氧增加了发酵，但并未改变线粒体生物合成或内皮细胞的有氧呼吸能力。在内皮细胞中，低氧导致碳水化合物、脂肪酸和氨基酸氧化过程中线粒体呼吸普遍下降，但仅增加了生酮氨基酸氧化。低氧诱导细胞内和线粒体内活性氧（ROS）生成增加，尽管细胞活力未变且抗氧化系统（超氧化物歧化酶SOD1和SOD2以及解偶联蛋白（UCPs））未增加。在低氧细胞的线粒体中，在呼吸链水平观察到相反的变化，即复合体II的表达和活性显著升高，而复合体I的表达和活性降低。复合体II活性的升高导致琥珀酸维持的线粒体内ROS生成增加，主要是通过增加逆向电子传递。还观察到低氧诱导的UCP2表达和活性降低。可以得出结论，长期暴露于低氧环境会导致从有氧分解代谢向无氧分解代谢的转变。低氧诱导的细胞内和线粒体内ROS生成增加并不过度，可能参与了低氧反应的内皮信号传导。我们的结果表明琥珀酸、复合体II和逆向电子传递在低氧诱导的内皮细胞调节中起重要作用。
