Respiratory gases and the regulation of transcription

Oxygen and carbon dioxide are the substrate and product of aerobic metabolism, respectively. Thus, the levels of these physiological gases are inextricably linked in physiological and pathophysiological conditions. Increased mitochondrial consumption of O-2 (to produce ATP) will produce more CO2. Furthermore, in lung pathologies such as chronic obstructive pulmonary disease, sleep apnoea and central hypoventilation syndrome, hypoxia and hypercapnia are co-incident. Acute responses to hypoxia involve carotid body-mediated changes in the rate and depth of breathing. Chronic adaptation to hypoxia involves a multitude of changes on a transcriptional level, which simultaneously increases oxygen utilization (via hypoxia-inducible factor and others), while suppressing superfluous energy-demanding processes. Acute responses to CO2 affect breathing primarily via central chemoreceptors. The nature of hypercapnia-dependent transcriptional regulation is an emerging area of research, but at present the mechanisms underpinning this response are not fully characterized and understood. Thus, given the juxtaposition of hypoxia and hypercapnia in health and disease, this manuscript reviews the current evidence for transcriptional responses to hypoxia and hypercapnia. Finally, we discuss the potential cross-talk between hypoxia and hypercapnia on a transcriptional level.