Respiratory gases and the regulation of transcription

Review Article , Eoin P. CumminsCiara E. Keogh , Exp Physiol, 2016 Aug 1;101(8):986-1002. doi: 10.1113/EP085715.

What is the topic of this review? This review highlights the transcriptional consequences for decreased cellular O2 levels (hypoxia) and increased cellular CO2 levels (hypercapnia). What advances does it highlight? We discuss recent advances in our understanding of the cellular response to hypoxia and consider the potential cross-talk between O2 – and CO2 -dependent transcriptional regulation. 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 O2 (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.

This is an EMERGING area of research!!!!

Could it help us to understand how Paula is alive and thriving exchanging only 1.5 L of air????

……… [that is her minute ventilation [Respiratory Rate [3] times Tidal Volume [a very respectable .5 L ] = 1.5 L ………….. [not the assumed 6-8 L].

Assumptions [scientific or otherwise] makes fools out of you and me.

Measurement is the key to scientific and medical knowledge.

Routine measurements of the pattern of vital signs [RR,BP,HR, and Body Temp.] at rest when awake….in health and in acute and chronic illness has not been studied before, except for Dr Emile Kraepelin in the 1900’s…..who studied the vital signs of thousands of patients with respiratory defects/injuries during attacks of manic depressive insanity [or as we see it, prolonged stages of delirium causing much anguish, distress, euphoria, irritability, etc….due to inability to clear CO2 from the blood by normal means [the nervous system reflexes of the ventilatory system to increase RR are broken].

Learning more about the regulation of the transcription of respiratory gases in people with ventilatory defect/injuries is a start.

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