Pulsed high oxygen induces a hypoxic-like response in human umbilical endothelial cells and in humans
Pulsed high oxygen induces a hypoxic-like response in human umbilical endothelial cells and in humans
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DOI：
10.1152/japplphysiol.00922.2012
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发表时间：
2012-12-01
影响因子：
3.3
通讯作者：
Virgili, F.
中科院分区：
文献类型：
--
作者：
Cimino, F.;Balestra, C.;Virgili, F.
Cimino F、Balestra C、Germonpre P、De Bels D、Tillmans F、Saija A、Speciale A、Virgili F。脉冲高氧会在人类脐带内皮细胞和人体中诱导缺氧样反应。 J Appl Physiol 113: 1684-1689, 2012。首次发表于 2012 年 10 月 4 日； doi: 10.1152/japplphyol.00922.2012.-有人提出，氧气利用率的相对变化，而不是稳态缺氧或高氧条件，在缺氧诱导因子 (HIF) 转录效应中发挥重要作用。根据描述“常压氧悖论”的假设，高氧事件后的正常氧含量被组织感知为缺氧，从而上调 HIF-1 活性。为了在细胞和功能水平上确认高氧事件后的含氧量正常被“解释”为缺氧事件，我们报告了一系列实验，研究了间歇性增加氧浓度对培养的人脐静脉内皮细胞中 HIF-1 水平和特定氧调节蛋白活性水平的影响，以及间歇呼吸后血红蛋白水平的影响 人体体内常压高（100%）和低（15%）氧。我们的实验证实，在高氧恢复期间，人脐静脉内皮细胞中 HIF 表达增加，与基质金属蛋白酶活性增加相关。这些数据表明，内皮细胞将高氧后恢复正常氧“解释”为低氧刺激。在功能层面，我们的数据显示，每隔一天呼吸 15% 和 100% 氧气 30 分钟，持续 10 天会导致人体血红蛋白水平增加。停止吸氧后，这种效果会增强。这些结果表明，高氧后组织氧张力的突然降低可能会触发促红细胞生成素的合成，从而证实了“相对”低氧是 HIF 介导的基因表达的有效刺激剂的假设。
Cimino F, Balestra C, Germonpre P, De Bels D, Tillmans F, Saija A, Speciale A, Virgili F. Pulsed high oxygen induces a hypoxic-like response in human umbilical endothelial cells and in humans. J Appl Physiol 113: 1684-1689, 2012. First published October 4, 2012; doi: 10.1152/japplphysiol.00922.2012.-It has been proposed that relative changes of oxygen availability, rather than steady-state hypoxic or hyperoxic conditions, play an important role in hypoxia-inducible factor (HIF) transcriptional effects. According to this hypothesis describing the "normobaric oxygen paradox", normoxia following a hyperoxic event is sensed by tissues as an oxygen shortage, upregulating HIF-1 activity. With the aim of confirming, at cellular and at functional level, that normoxia following a hyperoxic event is "interpreted" as a hypoxic event, we report a combination of experiments addressing the effects of an intermittent increase of oxygen concentration on HIF-1 levels and the activity level of specific oxygen-modulated proteins in cultured human umbilical vein endothelial cells and the effects of hemoglobin levels after intermittent breathing of normobaric high (100%) and low (15%) oxygen in vivo in humans. Our experiments confirm that, during recovery after hyperoxia, an increase of HIF expression occurs in human umbilical vein endothelial cells, associated with an increase of matrix metalloproteinases activity. These data suggest that endothelial cells "interpret" the return to normoxia after hyperoxia as a hypoxic stimulus. At functional level, our data show that breathing both 15 and 100% oxygen 30 min every other day for a period of 10 days induces an increase of hemoglobin levels in humans. This effect was enhanced after the cessation of the oxygen breathing. These results indicate that a sudden decrease in tissue oxygen tension after hyperoxia may act as a trigger for erythropoietin synthesis, thus corroborating the hypothesis that "relative" hypoxia is a potent stimulator of HIF-mediated gene expressions.