Haddad John J
Severinghaus-Radiometer Research Laboratories, University of California, San Francisco, CA, USA.
Biochem Biophys Res Commun. 2004 Apr 16;316(4):969-77. doi: 10.1016/j.bbrc.2004.02.162.
What is the nature of the oxygen sensor(s) and how do organisms sense variations in oxygen? A progressive rise of oxidative stress due to the altered reduction-oxidation (redox) homeostasis appears to be one of the hallmarks of the processes that regulate gene transcription. Dynamic changes in oxygen homeostasis and its close association with redox equilibrium, therefore, constitute a signaling mechanism for the expression/activation of oxygenes. This variation subsequently regulates the compartmentalization and functioning of HIF-1alpha and NF-kappaB. In addition, oxygen-evoked regulation of HIF-1alpha and NF-kappaB is closely coupled with intracellular redox state, such that modulating redox equilibrium affects their responsiveness at the molecular level (expression/transactivation). Interestingly, are these particular transcription factors potential oxygen sensors? The basic components of the intracellular oxidative/redox machinery and its crucial regulation of oxygen- and redox-sensitive transcription factors may help understand the network of oxygen sensing mechanisms and redox-related pathways.
氧传感器的本质是什么,生物体又是如何感知氧气变化的?由于氧化还原稳态改变导致的氧化应激逐渐增加,似乎是调节基因转录过程的标志之一。因此,氧稳态的动态变化及其与氧化还原平衡的密切关联,构成了一种用于氧相关基因表达/激活的信号传导机制。这种变化随后调节缺氧诱导因子-1α(HIF-1α)和核因子κB(NF-κB)的区室化及功能。此外,氧气引发的对HIF-1α和NF-κB的调节与细胞内氧化还原状态紧密相关,以至于调节氧化还原平衡会在分子水平(表达/反式激活)影响它们的反应性。有趣的是,这些特定的转录因子是潜在的氧传感器吗?细胞内氧化/还原机制的基本组成部分及其对氧和氧化还原敏感转录因子的关键调节,可能有助于理解氧传感机制和氧化还原相关途径的网络。