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首页> 外文期刊>Molecular and Cellular Biology >Transcription Factor HIF-1 Is a Necessary Mediator of the Pasteur Effect in Mammalian Cells
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Transcription Factor HIF-1 Is a Necessary Mediator of the Pasteur Effect in Mammalian Cells

机译：转录因子HIF-1是哺乳动物细胞中巴斯德效应的必要介体。

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摘要

The ability to respond to differential levels of oxygen is important to all respiring cells. The response to oxygen deficiency, or hypoxia, takes many forms and ranges from systemic adaptations to those that are cell autonomous. Perhaps the most ancient of the cell-autonomous adaptations to hypoxia is a metabolic one: the Pasteur effect, which includes decreased oxidative phosphorylation and an increase in anaerobic fermentation. Because anaerobic fermentation produces far less ATP than oxidative phosphorylation per molecule of glucose, increased activity of the glycolytic pathway is necessary to maintain free ATP levels in the hypoxic cell. Here, we present genetic and biochemical evidence that, in mammalian cells, this metabolic switch is regulated by the transcription factor HIF-1. As a result, cells lacking HIF-1α exhibit decreased growth rates during hypoxia, as well as decreased levels of lactic acid production and decreased acidosis. We show that this decrease in glycolytic capacity results in dramatically lowered free ATP levels in HIF-1α-deficient hypoxic cells. Thus, HIF-1 activation is an essential control element of the metabolic state during hypoxia; this requirement has important implications for the regulation of cell growth during development, angiogenesis, and vascular injury.
机译：对不同水平的氧气作出反应的能力对所有呼吸细胞都很重要。对缺氧或缺氧的反应有多种形式和范围，从系统适应到细胞自主适应。也许最古老的对缺氧的细胞自主适应是一种新陈代谢：巴斯德效应，包括氧化磷酸化的降低和厌氧发酵的增加。因为厌氧发酵产生的ATP比每个葡萄糖分子的氧化磷酸化少得多，所以糖酵解途径的活性增加对于维持低氧细胞中的游离ATP水平是必要的。在这里，我们提供了遗传和生物化学证据，在哺乳动物细胞中，这种代谢转换受转录因子HIF-1调控。结果，缺乏HIF-1α的细胞在缺氧期间表现出降低的生长速度，以及乳酸生成水平的降低和酸中毒的降低。我们表明，这种糖酵解能力的下降导致HIF-1α缺氧缺氧细胞中的游离ATP水平大大降低。因此，HIF-1激活是缺氧过程中代谢状态的重要控制因素。该要求对发育，血管生成和血管损伤期间细胞生长的调节具有重要意义。

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