Cellfood™ improves respiratory metabolism of endothelial cells and inhibits hypoxia-induced reactive oxygen species (ros) generation.
Cellfood™ improves respiratory metabolism of endothelial cells and inhibits hypoxia-induced reactive oxygen species (ros) generation.
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发表时间：
2011-06
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通讯作者：
E. Ferrero;A. Fulgenzi;D. Belloni;C. Foglieni;M. Ferrero
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作者：
E. Ferrero;A. Fulgenzi;D. Belloni;C. Foglieni;M. Ferrero
内皮细胞线粒体是ATP产生的主要场所，调节细胞内活性氧（ROS）的动态，进而控制内皮功能。内皮细胞（EC）需要充足的氧（O（2））供应。缺氧和高氧都可能促进ROS的过度产生，导致氧化应激、线粒体损伤和内皮功能障碍。我们研究了Cellfood™（CF），一种抗氧化化合物，在体外调节EC中O（2）可用性和线粒体呼吸代谢以及调节缺氧产生的ROS的能力和机制。用Clark电极测定人脐静脉内皮细胞（HUVEC）和ECV-304的O（2）消耗量。在加入CF后的最初几分钟内，O（2）消耗率上升，这与线粒体氧化能力的增加和良好的细胞活力有关。当EC暴露于CF长达8天时，观察到类似的行为。O（2）消耗增加，同时伴随着细胞内ATP含量的升高和LDH浓度的维持。CF通过上调MnSOD（一种负责线粒体功能保护的抗氧化剂）的表达，显著抑制缺氧诱导的ROS生成。EC缺氧反应由缺氧主调节因子HIF-1 α介导，其激活被CF减弱，伴随MnSOD上调。我们的研究结果表明，CF在改善呼吸代谢和激活EC中的抗氧化机制，从而保护内皮功能中的作用。
Endothelial mitochondria, the major site of ATP generation, modulate the intracellular dynamics of reactive oxygen species (ROS), which, in turn, control endothelial function. Adequate oxygen (O(2)) supply is required by endothelial cells (EC). Both hypoxia and hyperoxia may favor the overproduction of ROS leading to oxidative stress, mitochondrial damage and endothelial dysfunction. We investigated the capability and mechanisms of Cellfood™ (CF), an antioxidant compound, to modulate O(2) availability and mitochondrial respiratory metabolism and to regulate ROS generated by hypoxia in EC in vitro. Human umbilical vein endothelial cells (HUVEC) and ECV-304 were evaluated for the O(2) consumption using a Clark's electrode. The O(2) consumption rate rose, during the first minutes after CF addition and was associated with increase in mitochondrial oxidative capacity and good cell viability. Similar behaviours were observed when EC were exposed to CF for up to 8 days. The O(2) consumption increased and was accompanied by both intracellular rise of ATP and maintainment of LDH concentration. Hypoxia-induced ROS generation was significantly inhibited by CF, through the up-regulated expression of MnSOD, an anti-oxidant responsible for mitochondrial function preservation. The EC hypoxic response is mediated by the hypoxia master regulator HIF-1alpha whose activation was attenuated by CF, in concomitance with MnSOD up-regulation. Our results suggest a role for CF in improoving respiratory metabolism and in activating anti-oxidant mechanisms in EC, thus preserving endothelial function.