Regulation of gene expression by carbon dioxide

摘要

Carbon dioxide (CO_2 ) is a physiological gas found at low levels in the atmosphere and produced in cells during the process of aerobic respiration. Consequently, the levels of CO_2 within tissues are usually significantly higher than those found externally. Shifts in tissue levels of CO_2 (leading to either hypercapnia or hypocapnia) are associated with a number of pathophysiological conditions in humans and can occur naturally in niche habitats such as those of burrowing animals. Clinical studies have indicated that such altered CO_2 levels can impact upon disease progression. Recent advances in our understanding of the biology of CO_2 has shown that like other physiological gases such as molecular oxygen (O2) and nitric oxide (NO), CO_2 levels can be sensed by cells resulting in the initiation of physiological and pathophysiological responses. Acute CO_2 sensing in neurons and peripheral and central chemoreceptors is important in rapidly activated responses including olfactory signalling, taste sensation and cardiorespiratory control. Furthermore, a role for CO_2 in the regulation of gene transcription has recently been identified with exposure of cells and model organisms to high CO_2 leading to suppression of genes involved in the regulation of innate immunity and inflammation. This latter, transcriptional regulatory role for CO_2 , has been largely attributed to altered activity of the NF-kB family of transcription factors. Here, we review our evolving understanding of how CO_2 impacts upon gene transcription.